RBCC

Full text data of EMD

EMD (EDMD, STA) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Emerin

UniProt P50402
ID EMD_HUMAN Reviewed; 254 AA.
AC P50402; Q6FI02;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Emerin;
GN Name=EMD; Synonyms=EDMD, STA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=7894480; DOI=10.1038/ng1294-323;
RA Bione S., Maestrini E., Rivella S., Mancini M., Regis S., Romeo G.,
RA Toniolo D.;
RT "Identification of a novel X-linked gene responsible for Emery-
RT Dreifuss muscular dystrophy.";
RL Nat. Genet. 8:323-327(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8733135; DOI=10.1093/hmg/5.5.659;
RA Chen E.Y., Zollo M., Mazzarella R.A., Ciccodicola A., Chen C.-N.,
RA Zuo L., Heiner C., Burough F.W., Ripetto M., Schlessinger D.,
RA D'Urso M.;
RT "Long-range sequence analysis in Xq28: thirteen known and six
RT candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and
RT G6PD loci.";
RL Hum. Mol. Genet. 5:659-668(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8655156; DOI=10.1007/s004390050119;
RA Yamada T., Kobayashi T.;
RT "A novel emerin mutation in a Japanese patient with Emery-Dreifuss
RT muscular dystrophy.";
RL Hum. Genet. 97:693-694(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8595407; DOI=10.1093/hmg/4.10.1859;
RA Bione S., Small K., Aksmanovic M.A., D'Urso M., Ciccodicola A.,
RA Merlini L., Morandi L., Kress W., Yates J.R.W., Warren S.T.,
RA Toniolo D.;
RT "Identification of new mutations in the Emery-Dreifuss muscular
RT dystrophy gene and evidence for genetic heterogeneity of the
RT disease.";
RL Hum. Mol. Genet. 4:1859-1863(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 1-17.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [11]
RP PROTEIN SEQUENCE OF 1-31; 37-45; 48-115 AND 158-203, ACETYLATION AT
RP MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma, and Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=9673989; DOI=10.1016/S0960-8966(98)00031-5;
RA Squarzoni S., Sabatelli P., Ognibene A., Toniolo D., Cartegni L.,
RA Cobianchi F., Petrini S., Merlini L., Maraldi N.M.;
RT "Immunocytochemical detection of emerin within the nuclear matrix.";
RL Neuromuscul. Disord. 8:338-344(1998).
RN [13]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=9472006;
RA Ellis J.A., Craxton M., Yates J.R.W., Kendrick-Jones J.;
RT "Aberrant intracellular targeting and cell cycle-dependent
RT phosphorylation of emerin contribute to the Emery-Dreifuss muscular
RT dystrophy phenotype.";
RL J. Cell Sci. 111:781-792(1998).
RN [14]
RP INTERACTION WITH BANF1.
RX PubMed=11792822;
RA Haraguchi T., Koujin T., Segura-Totten M., Lee K.K., Matsuoka Y.,
RA Yoneda Y., Wilson K.L., Hiraoka Y.;
RT "BAF is required for emerin assembly into the reforming nuclear
RT envelope.";
RL J. Cell Sci. 114:4575-4585(2001).
RN [15]
RP INTERACTION WITH YTHDC1.
RX PubMed=12755701; DOI=10.1046/j.1432-1033.2003.03617.x;
RA Wilkinson F.L., Holaska J.M., Zhang Z., Sharma A., Manilal S.,
RA Holt I., Stamm S., Wilson K.L., Morris G.E.;
RT "Emerin interacts in vitro with the splicing-associated factor, YT521-
RT B.";
RL Eur. J. Biochem. 270:2459-2466(2003).
RN [16]
RP INTERACTION WITH GMCL.
RX PubMed=12493765; DOI=10.1074/jbc.M208811200;
RA Holaska J.M., Lee K.K., Kowalski A.K., Wilson K.L.;
RT "Transcriptional repressor germ cell-less (GCL) and barrier to
RT autointegration factor (BAF) compete for binding to emerin in vitro.";
RL J. Biol. Chem. 278:6969-6975(2003).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [18]
RP INTERACTION WITH BCLAF1, AND CHARACTERIZATION OF VARIANT EDMD1 PHE-54.
RX PubMed=15009215; DOI=10.1111/j.1432-1033.2004.04007.x;
RA Haraguchi T., Holaska J.M., Yamane M., Koujin T., Hashiguchi N.,
RA Mori C., Wilson K.L., Hiraoka Y.;
RT "Emerin binding to Btf, a death-promoting transcriptional repressor,
RT is disrupted by a missense mutation that causes Emery-Dreifuss
RT muscular dystrophy.";
RL Eur. J. Biochem. 271:1035-1045(2004).
RN [19]
RP FUNCTION, INTERACTION WITH ACTB; SPTAN1 AND F-ACTIN, MUTAGENESIS OF
RP SER-196 AND SER-197, AND CHARACTERIZATION OF VARIANTS EDMD1 PHE-54;
RP HIS-133 AND HIS-183.
RX PubMed=15328537; DOI=10.1371/journal.pbio.0020231;
RA Holaska J.M., Kowalski A.K., Wilson K.L.;
RT "Emerin caps the pointed end of actin filaments: evidence for an actin
RT cortical network at the nuclear inner membrane.";
RL PLoS Biol. 2:1354-1362(2004).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [22]
RP FUNCTION, AND INTERACTION WITH CTNNB1.
RX PubMed=16858403; DOI=10.1038/sj.emboj.7601230;
RA Markiewicz E., Tilgner K., Barker N., van de Wetering M., Clevers H.,
RA Dorobek M., Hausmanowa-Petrusewicz I., Ramaekers F.C.S.,
RA Broers J.L.V., Blankesteijn W.M., Salpingidou G., Wilson R.G.,
RA Ellis J.A., Hutchison C.J.;
RT "The inner nuclear membrane protein emerin regulates beta-catenin
RT activity by restricting its accumulation in the nucleus.";
RL EMBO J. 25:3275-3285(2006).
RN [23]
RP PHOSPHORYLATION AT SER-49, SUBCELLULAR LOCATION, INTERACTION WITH
RP LMNA, MASS SPECTROMETRY, AND MUTAGENESIS OF SER-49.
RX PubMed=16972941; DOI=10.1111/j.1742-4658.2006.05464.x;
RA Roberts R.C., Sutherland-Smith A.J., Wheeler M.A., Jensen O.N.,
RA Emerson L.J., Spiliotis I.I., Tate C.G., Kendrick-Jones J.,
RA Ellis J.A.;
RT "The Emery-Dreifuss muscular dystrophy associated-protein emerin is
RT phosphorylated on serine 49 by protein kinase A.";
RL FEBS J. 273:4562-4575(2006).
RN [24]
RP FUNCTION.
RX PubMed=16680152; DOI=10.1038/nature04682;
RA Jacque J.-M., Stevenson M.;
RT "The inner-nuclear-envelope protein emerin regulates HIV-1
RT infectivity.";
RL Nature 441:641-645(2006).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BETA-TUBULIN.
RX PubMed=17785515; DOI=10.1083/jcb.200702026;
RA Salpingidou G., Smertenko A., Hausmanowa-Petrucewicz I., Hussey P.J.,
RA Hutchison C.J.;
RT "A novel role for the nuclear membrane protein emerin in association
RT of the centrosome to the outer nuclear membrane.";
RL J. Cell Biol. 178:897-904(2007).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49; SER-54; SER-60 AND
RP SER-87, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH LMNA.
RX PubMed=19323649; DOI=10.1042/BC20080175;
RA Capanni C., Del Coco R., Mattioli E., Camozzi D., Columbaro M.,
RA Schena E., Merlini L., Squarzoni S., Maraldi N.M., Lattanzi G.;
RT "Emerin-prelamin A interplay in human fibroblasts.";
RL Biol. Cell 101:541-554(2009).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-8 AND SER-171, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [37]
RP STRUCTURE BY NMR OF 2-54.
RX PubMed=11470279; DOI=10.1016/S0014-5793(01)02649-7;
RA Wolff N., Gilquin B., Courchay K., Callebaut I., Worman H.J.,
RA Zinn-Justin S.;
RT "Structural analysis of emerin, an inner nuclear membrane protein
RT mutated in X-linked Emery-Dreifuss muscular dystrophy.";
RL FEBS Lett. 501:171-176(2001).
RN [38]
RP STRUCTURE BY NMR OF 2-54.
RX PubMed=11435115; DOI=10.1016/S0969-2126(01)00611-6;
RA Laguri C., Gilquin B., Wolff N., Romi-Lebrun R., Courchay K.,
RA Callebaut I., Worman H.J., Zinn-Justin S.;
RT "Structural characterization of the LEM motif common to three human
RT inner nuclear membrane proteins.";
RL Structure 9:503-511(2001).
RN [39]
RP VARIANTS EDMD1 HIS-183 AND THR-183.
RX PubMed=10323252; DOI=10.1007/s004390050946;
RA Ellis J.A., Yates J.R.W., Kendrick-Jones J., Brown C.A.;
RT "Changes at P183 of emerin weaken its protein-protein interactions
RT resulting in X-linked Emery-Dreifuss muscular dystrophy.";
RL Hum. Genet. 104:262-268(1999).
RN [40]
RP VARIANT EDMD1 HIS-133.
RX PubMed=11587540; DOI=10.1006/bbrc.2001.5708;
RA Holt I., Clements L., Manilal S., Morris G.E.;
RT "How does a g993t mutation in the emerin gene cause Emery-Dreifuss
RT muscular dystrophy?";
RL Biochem. Biophys. Res. Commun. 287:1129-1133(2001).
CC -!- FUNCTION: Stabilizes and promotes the formation of a nuclear actin
CC cortical network. Stimulates actin polymerization in vitro by
CC binding and stabilizing the pointed end of growing filaments.
CC Inhibits beta-catenin activity by preventing its accumulation in
CC the nucleus. Acts by influencing the nuclear accumulation of beta-
CC catenin through a CRM1-dependent export pathway. Links centrosomes
CC to the nuclear envelope via a microtubule association. EMD and BAF
CC are cooperative cofactors of HIV-1 infection. Association of EMD
CC with the viral DNA requires the presence of BAF and viral
CC integrase. The association of viral DNA with chromatin requires
CC the presence of BAF and EMD. Required for proper localization of
CC non-farnesylated prelamin-A/C.
CC -!- SUBUNIT: Interacts with lamins A and C, BANF1, GMCL, BCLAF1 and
CC YTHDC1/YT521. Interacts with TMEM43; the interaction retains
CC emerin in the nuclear inner membrane. Interacts with SUN1 and SUN2
CC (By similarity). Interacts with ACTB, SPTAN1, F-actin, CTNNB1 and
CC beta-tubulin.
CC -!- INTERACTION:
CC Q9NYF8:BCLAF1; NbExp=3; IntAct=EBI-489887, EBI-437804;
CC P35222:CTNNB1; NbExp=3; IntAct=EBI-489887, EBI-491549;
CC Q99962:SH3GL2; NbExp=2; IntAct=EBI-489887, EBI-77938;
CC Q9D666:Sun1 (xeno); NbExp=4; IntAct=EBI-489887, EBI-6752574;
CC Q9UH99:SUN2; NbExp=3; IntAct=EBI-489887, EBI-1044964;
CC -!- SUBCELLULAR LOCATION: Nucleus inner membrane; Single-pass membrane
CC protein; Nucleoplasmic side. Nucleus outer membrane.
CC Note=Colocalized with BANF1 at the central region of the
CC assembling nuclear rim, near spindle-attachment sites. The
CC accumulation of different intermediates of prelamin-A/C (non-
CC farnesylated or carboxymethylated farnesylated prelamin-A/C) in
CC fibroblasts modify its localization in the nucleus.
CC -!- TISSUE SPECIFICITY: Skeletal muscle, heart, colon, testis, ovary
CC and pancreas.
CC -!- PTM: Found in four different phosphorylated forms, three of which
CC appear to be associated with the cell cycle.
CC -!- DISEASE: Emery-Dreifuss muscular dystrophy 1, X-linked (EDMD1)
CC [MIM:310300]: A form of Emery-Dreifuss muscular dystrophy, a
CC degenerative myopathy characterized by weakness and atrophy of
CC muscle without involvement of the nervous system, early
CC contractures of the elbows, Achilles tendons and spine, and
CC cardiomyopathy associated with cardiac conduction defects.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Contains 1 LEM domain.
CC -!- WEB RESOURCE: Name=EMD db; Note="EMD mutation database";
CC URL="http://www.dmd.nl/nmdb/index.php?select_db=EMD";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/EMD";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X82434; CAA57817.1; -; mRNA.
DR EMBL; L44140; AAA92645.1; -; Genomic_DNA.
DR EMBL; D64111; BAA10972.1; -; Genomic_DNA.
DR EMBL; X86810; CAA60500.1; -; Genomic_DNA.
DR EMBL; BT007401; AAP36065.1; -; mRNA.
DR EMBL; CR536536; CAG38773.1; -; mRNA.
DR EMBL; BX936346; CAI43228.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72742.1; -; Genomic_DNA.
DR EMBL; BC000738; AAH00738.1; -; mRNA.
DR PIR; S50834; S50834.
DR RefSeq; NP_000108.1; NM_000117.2.
DR UniGene; Hs.522823; -.
DR PDB; 1JEI; NMR; -; A=2-54.
DR PDB; 2ODC; NMR; -; I=2-47.
DR PDB; 2ODG; NMR; -; C=2-47.
DR PDBsum; 1JEI; -.
DR PDBsum; 2ODC; -.
DR PDBsum; 2ODG; -.
DR ProteinModelPortal; P50402; -.
DR SMR; P50402; 2-54.
DR DIP; DIP-34638N; -.
DR IntAct; P50402; 26.
DR MINT; MINT-266014; -.
DR STRING; 9606.ENSP00000358857; -.
DR PhosphoSite; P50402; -.
DR DMDM; 1706639; -.
DR PaxDb; P50402; -.
DR PeptideAtlas; P50402; -.
DR PRIDE; P50402; -.
DR DNASU; 2010; -.
DR Ensembl; ENST00000369842; ENSP00000358857; ENSG00000102119.
DR Ensembl; ENST00000594177; ENSP00000468971; ENSG00000268557.
DR GeneID; 2010; -.
DR KEGG; hsa:2010; -.
DR UCSC; uc004fkl.3; human.
DR CTD; 2010; -.
DR GeneCards; GC0XP153607; -.
DR HGNC; HGNC:3331; EMD.
DR HPA; CAB001545; -.
DR HPA; CAB002029; -.
DR HPA; HPA000609; -.
DR MIM; 300384; gene.
DR MIM; 310300; phenotype.
DR neXtProt; NX_P50402; -.
DR Orphanet; 98863; X-linked Emery-Dreifuss muscular dystrophy.
DR PharmGKB; PA27766; -.
DR eggNOG; NOG46326; -.
DR HOGENOM; HOG000081509; -.
DR HOVERGEN; HBG001099; -.
DR InParanoid; P50402; -.
DR KO; K12569; -.
DR OMA; SIAHYRP; -.
DR PhylomeDB; P50402; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR EvolutionaryTrace; P50402; -.
DR GeneWiki; Emerin; -.
DR GenomeRNAi; 2010; -.
DR NextBio; 8137; -.
DR PRO; PR:P50402; -.
DR ArrayExpress; P50402; -.
DR Bgee; P50402; -.
DR CleanEx; HS_EMD; -.
DR Genevestigator; P50402; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005637; C:nuclear inner membrane; NAS:BHF-UCL.
DR GO; GO:0005640; C:nuclear outer membrane; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0007077; P:mitotic nuclear envelope disassembly; TAS:Reactome.
DR GO; GO:0007084; P:mitotic nuclear envelope reassembly; TAS:Reactome.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0007517; P:muscle organ development; TAS:ProtInc.
DR GO; GO:0035414; P:negative regulation of catenin import into nucleus; IMP:BHF-UCL.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:BHF-UCL.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IMP:BHF-UCL.
DR GO; GO:0060828; P:regulation of canonical Wnt receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR Gene3D; 1.10.720.40; -; 1.
DR InterPro; IPR011015; LEM/LEM-like_dom.
DR InterPro; IPR003887; LEM_dom.
DR Pfam; PF03020; LEM; 1.
DR SMART; SM00540; LEM; 1.
DR SUPFAM; SSF63451; SSF63451; 1.
DR PROSITE; PS50954; LEM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Cardiomyopathy;
KW Complete proteome; Direct protein sequencing; Disease mutation;
KW Emery-Dreifuss muscular dystrophy; Membrane; Microtubule; Nucleus;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 254 Emerin.
FT /FTId=PRO_0000206140.
FT TRANSMEM 223 243 Helical; (Potential).
FT DOMAIN 1 45 LEM.
FT REGION 46 222 Interaction with F-actin (Probable).
FT REGION 168 186 Interaction with CTNNB1.
FT COMPBIAS 192 199 Poly-Ser.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 8 8 Phosphoserine.
FT MOD_RES 49 49 Phosphoserine; by PKA.
FT MOD_RES 54 54 Phosphoserine.
FT MOD_RES 60 60 Phosphoserine.
FT MOD_RES 87 87 Phosphoserine.
FT MOD_RES 161 161 Phosphotyrosine (By similarity).
FT MOD_RES 171 171 Phosphoserine.
FT VARIANT 54 54 S -> F (in EDMD1; no loss of binding to
FT F-actin, enhanced rate of actin
FT polymerization and loss of binding to
FT BCLAF1).
FT /FTId=VAR_005198.
FT VARIANT 133 133 Q -> H (in EDMD1; loss of binding to F-
FT actin).
FT /FTId=VAR_016016.
FT VARIANT 149 149 D -> H (in dbSNP:rs2070818).
FT /FTId=VAR_038433.
FT VARIANT 183 183 P -> H (in EDMD1; no loss of binding to
FT F-actin and enhanced rate of actin
FT polymerization).
FT /FTId=VAR_005199.
FT VARIANT 183 183 P -> T (in EDMD1).
FT /FTId=VAR_005200.
FT MUTAGEN 49 49 S->A: Abolishes phosphorylation. No
FT effect on targeting to nuclear envelope
FT nor on interaction with LMNA.
FT MUTAGEN 49 49 S->E: Mimics phosphorylation. No effect
FT on targeting to nuclear envelope nor on
FT interaction with LMNA.
FT MUTAGEN 196 196 S->A: No loss of binding to F-actin; when
FT associated with A-197.
FT MUTAGEN 197 197 S->A: No loss of binding to F-actin; when
FT associated with A-196.
FT TURN 4 6
FT HELIX 9 16
FT STRAND 17 19
FT HELIX 29 31
FT HELIX 32 37
FT HELIX 40 42
SQ SEQUENCE 254 AA; 28994 MW; EB62EDD59B7A044F CRC64;
MDNYADLSDT ELTTLLRRYN IPHGPVVGST RRLYEKKIFE YETQRRRLSP PSSSAASSYS
FSDLNSTRGD ADMYDLPKKE DALLYQSKGY NDDYYEESYF TTRTYGEPES AGPSRAVRQS
VTSFPDADAF HHQVHDDDLL SSSEEECKDR ERPMYGRDSA YQSITHYRPV SASRSSLDLS
YYPTSSSTSF MSSSSSSSSW LTRRAIRPEN RAPGAGLGQD RQVPLWGQLL LFLVFVIVLF
FIYHFMQAEE GNPF
//

MIM 300384
*RECORD*
*FIELD* NO
300384
*FIELD* TI
*300384 EMERIN; EMD
;;STA
*FIELD* TX

DESCRIPTION

The EMD gene encodes a ubiquitous protein, emerin, that is found along
read morethe nuclear rim of many cell types and is a member of the nuclear
lamina-associated protein family. Mutation in the EMD gene has been
found to cause the Emery-Dreifuss type of muscular dystrophy (EDMD;
310300).

CLONING

Bione et al. (1993) constructed a transcriptional map of the 2-Mb region
of Xq28 to which the Emery-Dreifuss muscular dystrophy locus had been
mapped by linkage studies. Within this region, they identified the STA
gene. Bione et al. (1994) determined that STA (EMD) encodes a 254-amino
acid protein, termed emerin, which lacks a signal peptide, contains a
long N-terminal domain, and is hydrophilic except for a highly
hydrophobic 20-amino acid sequence at the C-terminal region. It has
several putative phosphorylation sites and 1 potential glycosylation
site. Northern blot analysis demonstrated ubiquitous expression of a
major, approximately 1-kb transcript, with highest expression in
skeletal muscle and heart and abundant expression in other tissues,
including colon, testis, ovary, and placenta. Bione et al. (1994)
suggested that emerin belongs to a class of tail-anchored membrane
proteins of the secretory pathway involved in vesicular transport.

Manilal et al. (1996) developed a panel of 12 monoclonal antibodies to a
large fragment of emerin cDNA prepared by PCR and expressed as a
recombinant protein in E. coli. These antibodies detected 4 different
epitopes on emerin. All monoclonal antibodies recognized a 34-kD protein
in all tissues tested. Immunofluorescence and cell fractionation studies
confirmed that emerin is located in the nuclear membrane. Amino acid
sequence similarities and cellular localization suggested that emerin is
a member of the nuclear lamina-associated protein family.

Small et al. (1997) isolated and characterized the complete mouse emerin
gene. The 2.9-kb mouse emerin gene comprises 6 exons and encodes a
protein 73% identical to that of the human protein. As in the human, the
gene encodes a serine-rich protein similar to lamina-associated
protein-2 (LAP2; 188380) and shows critical LAP2 phosphorylation sites.

GENE FUNCTION

Cartegni et al. (1997) reported that emerin localizes to the inner
nuclear membrane via its hydrophobic C-terminal domain, but that in
heart and cultured cardiomyocytes, it is also associated with the
intercalated discs. They proposed a general role for emerin in membrane
anchorage to the cytoskeleton. In the nuclear envelope, emerin plays a
ubiquitous and indispensable role in association of the nuclear membrane
with the lamina. In heart, it is specifically located to desmosomes and
fasciae adherentes. Desmosomes and fasciae adherentes anchor
desmin-containing intermediate filaments and the bundles of sarcomeric
myofilaments, respectively. They consist of transmembrane adhesive
glycoproteins, members of the cadherin superfamily, and of cytoplasmic
proteins such as vinculin (193065), catenins, and actin-binding
proteins. Different assortments of the same or similar proteins in
desmosomes, fasciae adherentes, focal adhesions, and other adhesive
junctions seem to confer specific functions to ensure cell-cell
communication and tight adhesion between cells and to the extracellular
matrix. The role of this complex assortment of proteins is best
demonstrated by the existence of many genetic diseases that perturb
adhesion and in the heart by the dramatic consequences of plakoglobin
(gamma-catenin) knockout (Ruiz et al., 1996): plakoglobin -/- mice die
at midgestation due to rupture of the ventricles. In heart, the specific
localization of emerin to desmosomes and fasciae adherentes could
account for the characteristic conduction defects described in patients
with Emery-Dreifuss muscular dystrophy.

Yorifuji et al. (1997) likewise demonstrated that emerin is localized at
the inner nuclear membrane. Studies for ultrastructural localization of
the protein in human skeletal muscle and HeLa cells, using ultrathin
cryosections, showed that immune-labeled colloidal gold particles were
localized on the nucleoplasmic surface of the inner nuclear membrane,
but not on the nuclear pore. They interpreted their results as
indicating that emerin anchors at the inner nuclear membrane through the
hydrophobic stretch and protrudes from the hydrophilic region to the
nuclear plasm where it interacts with the nuclear lamina. They
speculated that emerin contributes to maintenance of the nuclear
structure and stability, as well as nuclear functions, particularly in
muscle tissues that have severe stress with rigorous
contraction-relaxation movements and calcium flux.

By mutation analysis, Lee et al. (2001) determined that several, but not
all, disease mutations in emerin map to a central lamin A (LMNA;
150330)-binding domain, and that mutations in this region disrupt
emerin-lamin A interaction. They also found that emerin binds directly
to BAF (BANF1; 603811), a DNA-bridging protein, and this binding
required conserved residues in the N-terminal LEM domain of emerin. The
disease-linked emerin proteins all remained active for BAF binding both
in vitro and in vivo.

Haraguchi et al. (2001) visualized colocalization between emerin and BAF
at the 'core' region of chromosomes during telophase in HeLa cells. An
emerin mutant defective in BAF binding in vitro failed to localize at
the core in vivo and subsequently failed to localize at the reformed
nuclear envelope. In HeLa cells expressing a BAF mutant that did not
show core localization, endogenous emerin failed to localize at the core
region during telophase and did not assemble into the nuclear envelope
during the subsequent interphase. This BAF mutant also dominantly
dislocalized LAP2-beta (188380) and lamin A from the nuclear envelope.
Haraguchi et al. (2001) concluded that BAF is required for the assembly
of emerin and A-type lamins at the reforming nuclear envelope during
telophase and may mediate their stability in the subsequent interphase.

Jacque and Stevenson (2006) examined susceptibility of primary
macrophages to human immunodeficiency virus (HIV)-1 infection following
short interfering RNA (siRNA)-mediated silencing of nuclear lamins and
several lamin-associated proteins. They found that silencing of emerin
and BAF prevented infection with HIV-1, but not murine leukemia virus,
by preventing integration of the virus into host DNA. Chromatin
immunoprecipitation analysis identified emerin and BAF as cooperative
cofactors of HIV-1, and mutation analysis showed that viral cDNA did not
associate with BAF defective in emerin binding or with emerin lacking
the LEM domain. Jacque and Stevenson (2006) concluded that HIV-1 cDNA,
upon entering the nucleus, must interact with emerin to contact
chromatin, and they suggested that molecules that prevent this
interaction might promote abortive HIV-1 infection of a cell.

Ho et al. (2013) demonstrated that ectopic expression of emerin, which
is mislocalized in Lmna-null and Lmna(N195K/N195K) (see 150330.0007)
mutant cells, restored nuclear translocation of the mechanosensitive
transcription factor megakaryoblastic leukemia-1 (MKL1; 606078) and
rescued actin dynamics. These data indicated that emerin is a crucial
modulator of actin polymerization and that loss of emerin from the
nuclear envelope causes disturbed actin dynamics and impaired MKL1
signaling. Ho et al. (2013) concluded that these and other findings
suggested a novel mechanism that could provide insight into the disease
etiology for the cardiac phenotype in many laminopathies, whereby lamin
A/C and emerin regulate gene expression through modulation of nuclear
and cytoskeletal actin polymerization.

GENE STRUCTURE

Bione et al. (1995) reported the sequence of the EMD gene, which is
2,100 bp long. The gene contains 6 exons.

MAPPING

Bione et al. (1994) identified the EMD gene on a transcriptional map of
Xq28.

MOLECULAR GENETICS

In 5 patients with X-linked Emery-Dreifuss muscular dystrophy (EDMD1;
310300), Bione et al. (1994) identified mutations in the EMD gene
(300384.0001-300384.0005). These mutations resulted in the loss of all
or part of the protein.

Ellis et al. (1999) stated that more than 70 different mutations had
been identified in the emerin gene. They described 2 missense mutations
involving proline-183: P183H (300384.0008) and P183T (300384.0009).
Biochemical analyses had demonstrated that the mobility and expression
levels of the mutant forms of emerin are indistinguishable from those of
wildtype emerin, but that they have weakened interactions with nuclear
lamina components.

In a large consanguineous Algerian family segregating isolated atrial
cardiac conduction defects and Emery-Dreifuss muscular dystrophy, Ben
Yaou et al. (2007) identified a deletion of lys37 (delK37) in the EMD
gene. Two men with EDMD were hemizygous for the mutation and homozygous
for an LMNA mutation (150330.0020). Three males who were hemizygous for
delK37 developed isolated atrial cardiac conduction defects in their
forties; 1 asymptomatic male carrier was 32 years old. Three of 5 women
heterozygous for delK37 also had cardiac disease. Ben Yaou et al. (2007)
stated that this was the first report of an EMD mutation giving rise to
isolated cardiac disease.

Brown et al. (2011) identified pathogenic mutations in the EMD gene in
23 (9.0%) of 255 North American patients referred for testing for EDMD.
There were 8 novel and 10 recurrent mutations. Most (90.5%) of the
mutations were predicted to result in a severely truncated or lack of
protein. Analysis of 130 EMD mutations indicated that exon 2 may be a
hotspot, perhaps owing to the high GC content.

ANIMAL MODEL

Frock et al. (2006) found that most cultured muscle cells from Lmna
knockout mice exhibited impaired differentiation kinetics and reduced
differentiation potential. Similarly, knockdown of Lmna or emerin
expression by RNA interference in normal muscle cells impaired
differentiation potential and reduced expression of muscle-specific
genes, Myod (159970) and desmin (125660). To determine whether impaired
myogenesis was linked to reduced Myod or desmin levels, Frock et al.
(2006) individually expressed these proteins in Lmna-null myoblasts and
found that both increased the differentiation potential of mutant
myoblasts. Frock et al. (2006) concluded that LMNA and emerin are
required for myogenic differentiation, at least in part, through an
effect on expression of critical myoblast proteins.

*FIELD* AV
.0001
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, 2-BP DEL, NT564

Bione et al. (1994) described deletion of nucleotides 564 and 565 in the
EMD gene in affected members of a family with Emery-Dreifuss muscular
dystrophy (310300). This resulted in a frameshift and a stop codon after
amino acid 207.

.0002
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, MET1VAL

In affected members of a family with Emery-Dreifuss muscular dystrophy
(310300), Bione et al. (1994) described an A-to-G transition at
nucleotide 59 of the EMD gene, abolishing the ATG methionine initiator
codon.

.0003
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, 29-BP DEL, NT113

In the affected members of a family with Emery-Dreifuss muscular
dystrophy (310300), Bione et al. (1994) found deletion of nucleotides
113 to 141 of the EMD gene, resulting in a frameshift and a stop codon
after amino acid 21.

.0004
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, 2-BP INS, NT198

In affected members of a family with Emery-Dreifuss muscular dystrophy
(310300), Bione et al. (1994) found insertion of 2 basepairs after
nucleotide 198 of the EMD gene, resulting in a frameshift and a stop
codon after amino acid 64.

.0005
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, IVSAS, A-G, -3, 214-BP INS

In affected members of a family with Emery-Dreifuss muscular dystrophy
(310300), Bione et al. (1994) found an A-to-G transition at the -3
position in a 3-prime splice junction of the EMD gene. The mutation was
first detected as an abnormality in the sequence of an RT-PCR product
which showed insertion of 214 bp at nucleotide 324. The nucleotide
sequence of the genomic fragments confirmed that the 214-bp insertion
was an unspliced intron. In the presence of the mutation, alternative
3-prime splice junctions were used at position -87 of the same intron
and position 365 in the next exon, giving 2 additional bands of size
intermediate between the normal and the band reflecting the 214-bp
insertion.

.0006
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, GLN43TER

Klauck et al. (1995) identified novel mutations in 3 families with
Emery-Dreifuss muscular dystrophy (310300). One of these was a C-to-T
transition at nucleotide 188, resulting in a change of codon 43 from CAG
(gln) to a stop codon.

.0007
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, 1-BP DEL, FS236TER

In a patient with Emery-Dreifuss muscular dystrophy (310300), Yamada and
Kobayashi (1996) found that the emerin gene carried a 1-bp deletion of C
at nucleotide 672 or 673. This deletion caused a frameshift leading to
change in the amino acid sequence (amino acids 206-235) and generating
an early stop codon.

.0008
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, PRO183HIS

In a man with Emery-Dreifuss muscular dystrophy (310300), Ellis et al.
(1999) identified a pro183-to-his mutation in the EMD gene, which they
called the STA gene. The patient was first referred to a neurologist at
age 31 because of back pain, weakness in the legs greater than the arms,
and leg numbness. As a child, he had been limited in his participation
in athletics in school. Upper limb weakness was noticed in childhood,
but no lower limb weakness was noted until age 25. He developed a
burning-quality low back pain at age 27 which radiated into the
posterior aspect of both legs. He had developed third-degree heart block
requiring a pacemaker. There were mild contractures of both ankles but
no elbow contractures.

.0009
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, PRO183THR

In a family with 4 brothers and a maternal cousin with Emery-Dreifuss
muscular dystrophy (310300), Ellis et al. (1999) identified a
pro183-to-thr mutation in the EMD gene, which they referred to as the
STA gene. Yates et al. (1999) identified the P183T mutation in a family
with an unusually mild EDMD phenotype and normal amounts of emerin.

.0010
EMERY-DREIFUSS MUSCULAR DYSTROPHY, X-LINKED
EMD, 5-BP DEL, NT631

In 2 brothers with Emery-Dreifuss muscular dystrophy (310300), Manilal
et al. (1998) identified a 5-bp deletion (TCTAC) spanning nucleotides
631-635 of the EMD gene.

*FIELD* SA
Boswinkel et al. (1985); Boyle et al. (2001); Consalez et al. (1991);
Hodgson et al. (1986); Nevo et al. (1999); Romeo et al. (1988); Thomas
et al. (1986); Wulff et al. (1997); Yates et al. (1986); Yates et
al. (1993)
*FIELD* RF
1. Ben Yaou, R.; Toutain, A.; Arimura, T.; Demay, L.; Massart, C.;
Peccate, C.; Muchir, A.; Llense, S.; Deburgreave, N.; Leturcq, F.;
Litim, K. E.; Rahmoun-Chiali, N.; Richard, P.; Babuty, D.; Recan-Budiartha,
D.; Bonne, G.: Multitissular involvement in a family with LMNA and
EMD mutations: role of digenic mechanism? Neurology 68: 1883-1894,
2007.

2. Bione, S.; Maestrini, E.; Rivella, S.; Mancini, M.; Regis, S.;
Romeo, G.; Toniolo, D.: Identification of a novel X-linked gene responsible
for Emery-Dreifuss muscular dystrophy. Nature Genet. 8: 323-327,
1994.

3. Bione, S.; Small, K.; Aksmanovic, V. M. A.; D'Urso, M.; Ciccodicola,
A.; Merlini, L.; Morandi, L.; Kress, W.; Yates, J. R. W.; Warren,
S. T.; Toniolo, D.: Identification of new mutations in the Emery-Dreifuss
muscular dystrophy gene and evidence for genetic heterogeneity of
the disease. Hum. Molec. Genet. 4: 1859-1863, 1995.

4. Bione, S.; Tamanini, F.; Maestrini, E.; Tribioli, C.; Poustka,
A.; Torri, G.; Rivella, S.; Toniolo, D.: Transcriptional organization
of a 450-kb region of the human X chromosome in Xq28. Proc. Nat.
Acad. Sci. 90: 10977-10981, 1993.

5. Boswinkel, E.; Walker, A.; Hodgson, S.; Benham, F.; Bobrow, M.;
Davies, K.; Dubowitz, V.; Grenata, C.: Linkage analysis using eight
DNA polymorphisms along the length of the X chromosome locates the
gene for Emery-Dreyfuss muscular dystrophy to distal Xq. (Abstract) Cytogenet.
Cell Genet. 40: 586 only, 1985.

6. Boyle, S.; Gilchrist, S.; Bridger, J. M.; Mahy, N. L.; Ellis, J.
A.; Bickmore, W. A.: The spatial organization of human chromosomes
within the nuclei of normal and emerin-mutant cells. Hum. Molec.
Genet. 10: 211-219, 2001.

7. Brown, C. A.; Scharner, J.; Felice, K.; Meriggioli, M. N.; Tarnopolsky,
M.; Bower, M.; Zammit, P. S.; Mendell, J. R.; Ellis, J. A.: Novel
and recurrent EMD mutations in patients with Emery-Dreifuss muscular
dystrophy, identify exon 2 as a mutation hotspot. J. Hum. Genet. 56:
589-594, 2011.

8. Cartegni, L.; Raffaele di Barletta, M.; Barresi, R.; Squarzoni,
S.; Sabatelli, P.; Maraldi, N.; Mora, M.; Di Blasi, C.; Cornelio,
F.; Merlini, L.; Villa, A.; Cobianchi, F.; Toniolo, D.: Heart-specific
localization of emerin: new insights into Emery-Dreifuss muscular
dystrophy. Hum. Molec. Genet. 6: 2257-2264, 1997.

9. Consalez, G. G.; Thomas, N. S. T.; Stayton, C. L.; Knight, S. J.
L.; Johnson, M.; Hopkins, L. C.; Harper, P. S.; Elsas, L. J.; Warren,
S. T.: Assignment of Emery-Dreifuss muscular dystrophy to the distal
region of Xq28: the results of a collaborative study. Am. J. Hum.
Genet. 48: 468-480, 1991.

10. Ellis, J. A.; Yates, J. R. W.; Kendrick-Jones, J.; Brown, C. A.
: Changes at P183 of emerin weaken its protein-protein interactions
resulting in X-linked Emery-Dreifuss muscular dystrophy. Hum. Genet. 104:
262-268, 1999.

11. Frock, R. L.; Kudlow, B. A.; Evans, A. M.; Jameson, S. A.; Hauschka,
S. D.; Kennedy, B. K.: Lamin A/C and emerin are critical for skeletal
muscle satellite cell differentiation. Genes Dev. 20: 486-500, 2006.

12. Haraguchi, T.; Koujin, T.; Segura-Totten, M.; Lee, K. K.; Matsuoka,
Y.; Yoneda, Y.; Wilson, K. L.; Hiraoka, Y.: BAF is required for emerin
assembly into the reforming nuclear envelope. J. Cell Sci. 114:
4575-4585, 2001.

13. Ho, C. Y.; Jaalouk, D. E.; Vartiainen, M. K.; Lammerding, J.:
Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin
dynamics. Nature 497: 507-511, 2013.

14. Hodgson, S. V.; Boswinkel, E.; Walker, A.; Bobrow, M.; Davies,
K.; Dubowitz, V.; Granata, G.; Merlini, L.: Linkage analysis using
nine DNA polymorphisms along the length of the X chromosome locates
the gene for Emery-Dreifuss muscular dystrophy to distal Xq. (Abstract) J.
Med. Genet. 23: 169-170, 1986.

15. Jacque, J.-M.; Stevenson, M.: The inner-nuclear-envelope protein
emerin regulates HIV-1 infectivity. Nature 441: 641-645, 2006.

16. Klauck, S.; Wilgenbus, P.; Yates, J. R. W.; Muller, C. R.; Poustka,
A.: Identification of novel mutations in three families with Emery-Dreifuss
muscular dystrophy. Hum. Molec. Genet. 4: 1853-1857, 1995.

17. Lee, K. K.; Haraguchi, T.; Lee, R. S.; Koujin, T.; Hiraoka, Y.;
Wilson, K. L.: Distinct functional domains in emerin bind lamin A
and DNA-bridging protein BAF. J. Cell Sci. 114: 4567-4573, 2001.

18. Manilal, S.; Nguyen thi Man; Sewry, C. A.; Morris, G. E.: The
Emery-Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane
protein. Hum. Molec. Genet. 5: 801-808, 1996.

19. Manilal, S.; Recan, D.; Sewry, C. A.; Hoeltzenbein, M.; Llense,
S.; Leturcq, F.; Deburgrave, N.; Barbot, J.-C.; Nguyen thi Man; Muntoni,
F.; Wehnert, M.; Kaplan, J.-C.; Morris, G. E.: Mutations in Emery-Dreifuss
muscular dystrophy and their effects on emerin protein expression. Hum.
Molec. Genet. 7: 855-864, 1998.

20. Nevo, Y.; Al-Lozi, M.; Parsadanian, A. S.; Elliott, J. L.; Connolly,
A. M.; Pestronk, A.: Mutation analysis in Emery-Dreifuss muscular
dystrophy. Pediat. Neurol. 21: 456-459, 1999.

21. Romeo, G.; Roncuzzi, L.; Sangiorgi, S.; Giacanelli, M.; Liguori,
M.; Tessarolo, D.; Rocchi, M.: Mapping of the Emery-Dreifuss gene
through reconstruction of crossover points in two Italian pedigrees. Hum.
Genet. 80: 59-62, 1988.

22. Ruiz, P.; Brinkmann, V.; Ledermann, B.; Behrend, M.; Grund, C.;
Thalhammer, C.; Vogel, F.; Birchmeier, C.; Gunthert, U.; Franke, W.
W.; Birchmeier, W.: Targeted mutation of plakoglobin in mice reveals
essential functions of desmosomes in the embryonic heart. J. Cell
Biol. 135: 215-225, 1996.

23. Small, K.; Wagener, M.; Warren, S. T.: Isolation and characterization
of the complete mouse emerin gene. Mammalian Genome 8: 337-341,
1997.

24. Thomas, N. S. T.; Williams, H.; Elsas, L. J.; Hopkins, L. C.;
Sarfarazi, M.; Harper, P. S.: Localisation of the gene for Emery-Dreifuss
muscular dystrophy to the distal long arm of the X chromosome. J.
Med. Genet. 23: 596-598, 1986.

25. Wulff, K.; Parrish, J. E.; Herrmann, F. H.; Wehnert, M.: Six
novel mutations in the emerin gene causing X-linked Emery-Dreifuss
muscular dystrophy. Hum. Mutat. 9: 526-530, 1997.

26. Yamada, T.; Kobayashi, T.: A novel emerin mutation in a Japanese
patient with Emery-Dreifuss muscular dystrophy. Hum. Genet. 97:
693-694, 1996.

27. Yates, J. R. W.; Affara, N. A.; Jamieson, D. M.; Ferguson-Smith,
M. A.; Hausmanowa-Petrusewicz, I.; Zaremba, J.; Borkowska, J.; Johnston,
A. W.; Kelly, K.: Emery-Dreifuss muscular dystrophy: localisation
to Xq27.3-qter confirmed by linkage to the factor VIII gene. J. Med.
Genet. 23: 587-590, 1986.

28. Yates, J. R. W.; Bagshaw, J.; Aksmanovic, V. M. A.; Coomber, E.;
McMahon, R.; Whittaker, J. L.; Morrison, P. J.; Kendrick-Jones, J.;
Ellis, J. A.: Genotype-phenotype analysis in X-linked Emery-Dreifuss
muscular dystrophy and identification of a missense mutation associated
with a milder phenotype. Neuromusc. Disord. 9: 159-165, 1999.

29. Yates, J. R. W.; Warner, J. P.; Smith, J. A.; Deymeer, F.; Azulay,
J.-P.; Hausmanowa-Petrusewicz, I.; Zaremba, J.; Borkowska, J.; Affara,
N. A.; Ferguson-Smith, M. A.: Emery-Dreifuss muscular dystrophy:
linkage to markers in distal Xq28. J. Med. Genet. 30: 108-111, 1993.

30. Yorifuji, H.; Tadano, Y.; Tsuchiya, Y.; Ogawa, M.; Goto, K.; Umetani,
A.; Asaka, Y.; Arahata, K.: Emerin, deficiency of which causes Emery-Dreifuss
muscular dystrophy, is localized at the inner nuclear membrane. Neurogenetics 1:
135-140, 1997.

*FIELD* CN
Ada Hamosh - updated: 07/11/2013
Cassandra L. Kniffin - updated: 9/19/2011
Cassandra L. Kniffin - updated: 1/30/2008
Paul J. Converse - updated: 6/19/2006
Patricia A. Hartz - updated: 3/28/2006
Patricia A. Hartz - updated: 5/19/2003

*FIELD* CD
Cassandra L. Kniffin: 3/26/2002

*FIELD* ED
alopez: 07/11/2013
carol: 10/4/2011
ckniffin: 9/19/2011
alopez: 4/12/2011
wwang: 3/22/2010
carol: 1/5/2010
wwang: 2/1/2008
ckniffin: 1/30/2008
mgross: 6/19/2006
wwang: 3/29/2006
terry: 3/28/2006
mgross: 5/19/2003
carol: 4/5/2002
ckniffin: 4/2/2002
carol: 4/2/2002
ckniffin: 3/29/2002

MIM 310300
*RECORD*
*FIELD* NO
310300
*FIELD* TI
#310300 EMERY-DREIFUSS MUSCULAR DYSTROPHY 1, X-LINKED; EDMD1
;;EMD1;;
MUSCULAR DYSTROPHY, TARDIVE, DREIFUSS-EMERY TYPE, WITH CONTRACTURES;;
read moreSCAPULOPERONEAL SYNDROME, X-LINKED, FORMERLY;;
HUMEROPERONEAL NEUROMUSCULAR DISEASE, FORMERLY
*FIELD* TX
A number sign (#) is used with this entry because X-linked
Emery-Dreifuss muscular dystrophy-1 (EDMD1) is caused by mutation in the
gene encoding emerin (EMD; 300384).

DESCRIPTION

Emery-Dreifuss muscular dystrophy is a degenerative myopathy
characterized by weakness and atrophy of muscle without involvement of
the nervous system. Flexion deformities of the elbows dating from early
childhood, mild pectus excavatum, signs of cardiac involvement and
absence of muscle pseudohypertrophy, involvement of the forearm muscles,
and mental retardation distinguish the Emery-Dreifuss form (EDMD1) from
the Becker form (300376).

- Genetic Heterogeneity of Emery-Dreifuss Muscular Dystrophy

An autosomal dominant form of Emery-Dreifuss muscular dystrophy, EDMD2
(181350), is caused by mutation in the lamin A/C gene (LMNA; 150330); a
possible autosomal recessive form of the disorder that lacks cardiac
features (EDMD3; see 181350) may be caused by mutation in the LMNA gene
(150330.0014). Additional autosomal dominant forms include EDMD4
(612998), caused by mutation in the SYNE1 gene (608441), EDMD5 (612999),
caused by mutation in the SYNE2 gene (608442), and EDMD7 (614302),
caused by mutation in the TMEM43 gene (612048). A second X-linked form
(EDMD6; see 300696) is caused by mutation in the FHL1 gene (300163).

CLINICAL FEATURES

Dreifuss and Hogan (1961) and Emery and Dreifuss (1966) studied a
Virginia kindred in which there were 8 affected males in 3 generations
in a typical X-linked pedigree pattern. Onset of muscle weakness, first
affecting the lower extremities with a tendency to walk on the toes, was
noted around the age of 4 or 5 years. By the early teens, waddling gait
with increased lumbar lordosis was marked and weakness of the shoulder
girdle musculature appeared later. Slow progression with continued
gainful employment is the rule.

- Cardiac

The cardiac conduction defect in EDMD patients is the most serious and
life-threatening clinical manifestation of the disease.

Cardiac defects have been described in female carriers (Emery, 1989) in
the absence of any skeletal muscle abnormality, suggesting a prominent
role in cardiac conduction for emerin.

Becker (1972) republished illustrations of typical cases reported by
Cestan and LeJonne (1902). Dickey et al. (1984) reported a large kindred
in which adults, both male hemizygotes and female heterozygotes, had
lethal cardiac disease characterized especially by atrial arrhythmias.
Skinner and Emery (1974) pointed out that the serum creatine kinase of
carriers is elevated mainly in young women and gave a 'normal' curve for
carrier and noncarrier women.

After a period of 25 years, Emery (1987) reinvestigated the original
Virginia family. He confirmed that cardiomyopathy, presenting most often
as atrioventricular block, is a significant feature of the disease,
which is characterized by the triad of (1) slowly progressive muscle
wasting and weakness with humeroperoneal distribution in the early
stages; (2) early contractures of the elbows, Achilles tendons, and
postcervical muscles; and (3) cardiomyopathy.

Takahashi (1971) reported the same disorder as Mawatari and Katayama
(1973) in 2 brothers. Wright and Elsas (1980) provided genetic studies
of the kindred discussed by Waters et al. (1975). The onset was in the
teens, with total disability by the third decade and death by age 50.
Type I muscle fibers were affected, resulting in an unusual distribution
of atrophy in the proximal upper and distal lower limbs. Cardiac
conduction defects often preceded overt muscle atrophy. Cardiac signs
began with small P waves and prolonged PR intervals, and progressed to
complete AV heart block with bradycardiac idioventricular rhythms and
atrial paralysis requiring pacemaker implantation. Cardiac signs were
detected as early as age 12. The earliest pacemaker insertion was in a
20-year-old male who could still do heavy physical labor. In the absence
of gross muscle atrophy, he had markedly elevated creatine phosphokinase
(CPK) levels. In some, contractures at the elbows were evident as early
as age 13. Contractures also developed in the neck and Achilles tendons.

Buckley et al. (1999) investigated the cardiac status in 3 patients with
EDMD. The effect on the heart became apparent in the teenage years and
was characterized by cardiac conduction defects and infiltration of the
myocardium by fibrous and adipose tissue. It first affected the atria,
which resulted in atrial paralysis; treatment with ventricular pacing
was usually needed. The authors found that female carriers can develop
heart problems and are at risk of sudden death.

- Skeletal

Dubowitz (1973) gave the name rigid spine syndrome to the disorder in a
17-year-old boy with a myopathy and stiffness of the back and neck from
an early age and progressive scoliosis in his teens. For several years
he had had difficulty in extending his elbows. Creatine phosphokinase
was moderately elevated. Dubowitz (1973) made reference to 3 other
similar cases he had seen. Wettstein et al. (1983) suggested that this
may be an X-linked disorder and may be related to the Emery-Dreifuss
muscular dystrophy with contractures. Rigid spine syndrome (602771) is
distinguished from Emery-Dreifuss muscular dystrophy by lack of cardiac
involvement and autosomal recessive inheritance.

- Scapuloperoneal Syndrome

Although Davidenkow (1939) of Leningrad considered X-linked
scapuloperoneal syndrome to be a distinct disorder, many kindreds
reported to have an X-linked scapuloperoneal syndrome, or humeroperoneal
neuromuscular disease, have been determined to have Emery-Dreifuss
muscular dystrophy.

Under the designation scapuloperoneal syndrome, Thomas et al. (1972)
described a kindred with typical X-linked inheritance of a myopathy
manifesting as muscular weakness and wasting, affecting predominantly
the proximal muscles of the legs. Accompanying features were
contractures of the elbows, pes cavus, and, in adulthood,
cardiomyopathy. Pseudohypertrophy was absent. Close linkage with deutan
colorblindness (303800) was found. The authors pointed out similarities
to the Emery benign type of muscular dystrophy with contractures but
thought that the distribution of muscular involvement distinguished the
two. They later revised their opinion and concluded that the disorder is
in fact EDMD (Thomas and Petty, 1985).

Many studies reached the conclusion that X-linked scapuloperoneal
syndrome was the same condition as Emery-Dreifuss muscular dystrophy
(Rotthauwe et al., 1972; Mawatari and Katayama, 1973; Rowland et al.,
1979; Sulaiman et al., 1981; Thomas and Petty, 1985; Merlini et al.,
1986).

Goldblatt et al. (1989) presented clinical and molecular genetic
evidence that the Emery-Dreifuss syndrome and X-linked muscular
dystrophy with contractures are genetically homogeneous.

Emery (1989) insisted that the designation scapuloperoneal syndrome
should be reserved for an autosomal dominant disorder that can be either
myopathic (181430) or more often neuropathic (181400), has later onset
(in adulthood) with late development of contractures, and does not show
cardiac conduction defects.

- Limb-Girdle Presentation

Ura et al. (2007) reported 2 unrelated males with EDMD confirmed by
genetic analysis who presented with limb-girdle muscular dystrophy. The
first patient was a 9-year-old boy who developed proximal muscle
weakness and atrophy of the lower limbs, waddling gait, and lordotic
posture by age 6. He had showed unsteady gait at age 4. Serum creatine
kinase was increased and muscle biopsy showed moderate fiber size
variation, internalized nuclei, and absence of emerin staining.
Electrocardiogram revealed transient sinus arrhythmia. The second
patient was a 50-year-old man who noted progressive proximal muscle
weakness in the lower limbs beginning at age 35. He had waddling gait,
Gowers sign, and minimal joint contractures. Cardiac studies showed
valvular insufficiency and atrioventricular block. Ura et al. (2007)
noted that LMNA mutations, which can result in EDMD1, also underlie
LGMD1B (159001). The findings expanded the phenotypic features
associated with X-linked EDMD.

INHERITANCE

Emery-Dreifuss muscular dystrophy is inherited as an X-linked recessive
disorder. Although Rudenskaya et al. (1994) described Emery-Dreifuss
muscular dystrophy in 4 generations of a family and concluded that the
inheritance was autosomal dominant, the pedigree was also consistent
with X-linked dominant inheritance, since all daughters of affected
males were affected. The females may have been less severely affected;
one, aged 29 years, worked as a crane-driver. They also described 2
sporadic cases, both in males; 1 closely resembled rigid spine syndrome.
Rudenskaya et al. (1994) commented on the remarkable intra- and
interfamilial variation in the clinical manifestations of EDMD.

DIAGNOSIS

Manilal et al. (1996) showed that muscle biopsy from an EDMD patient
showed complete absence of emerin by both Western blotting and
immunohistology and suggested that a simple diagnostic antibody test may
be carried out for this disorder.

Nevo et al. (1999), who identified a different mutation in emerin in
each of 3 families with EDMD, emphasized the usefulness of early
diagnosis because insertion of a pacemaker may be life saving. They also
emphasized the finding of numerous private mutations, suggesting that
detection of the presence or absence of the emerin protein in tissues
may be more practical as a diagnostic tool than mutation screening.

Fujimoto et al. (1999) reported a case of X-linked EDMD in a 3-year-old
boy with contractures of the Achilles tendons, but without
characteristic contractures of the elbows and cardiac involvement. In
immunofluorescent staining of a muscle biopsy, no emerin was noted on
the nuclear membrane. RT-PCR and PCR-based genomic DNA analysis of the
emerin gene revealed no amplification products in the patient's samples.
The authors stressed that emerin staining should be part of the work-up
of every unexplained muscular dystrophy, because the early diagnosis of
EDMD is very important, especially to avoid cardiac complications that
may cause sudden death.

BIOCHEMICAL FEATURES

Pearson et al. (1965) found a difference of muscle LDH electrophoretic
pattern in this type as compared with the Duchenne type.

PATHOGENESIS

Emerin, the product of the EMD gene, is a ubiquitous protein that
decorates the nuclear rim of many cell types. These findings could not
explain, however, the role of emerin nor account for the skeletal
muscle- and heart-specific manifestations associated with the disorder.
Using 2 antisera against synthetic peptide fragments predicted from
emerin cDNA, Nagano et al. (1996) found positive nuclear membrane
staining in skeletal, cardiac, and smooth muscles in normal controls and
in patients with neuromuscular diseases other than EDMD. In contrast, a
deficiency in immunofluorescent staining of skeletal and cardiac muscle
from EDMD patients was observed.

In heart, the specific localization of emerin to desmosomes and fasciae
adherentes could account for the characteristic conduction defects
described in patients with Emery-Dreifuss muscular dystrophy (Cartegni
et al., 1997).

Manilal et al. (1999) found that affinity-purified antibodies against
emerin gave immunostaining only in the nuclear membrane, casting doubt
on the hypothesis that cardiac defects in EDMD are caused by absence of
emerin from intercalated discs (Cartegni et al., 1997). Although emerin
was abundant in the membranes of cardiomyocyte nuclei, it was absent
from any nonmyocyte cells in the heart. This distribution of emerin was
similar to that of lamin A (LMNA; 150330), which is mutant in the
autosomal Emery-Dreifuss syndromes (181350). In contrast, laminin B1
(LMNB1; 150340) was absent from cardiomyocyte nuclei, showing that lamin
B1 is not essential for localization of emerin to the nuclear lamina.
Lamin B1 was also almost completely absent from skeletal muscle nuclei.
Manilal et al. (1999) suggested that in EDMD the additional absence of
lamin B1 from heart and skeletal muscle nuclei that already lack emerin
may explain why these tissues are particularly affected. They further
suggested that a functional interaction between emerin and lamin A in
nuclei could explain the identical phenotype in the 2 forms of EDMD.

Using FISH and immunofluorescence, Boyle et al. (2001) analyzed the
nuclear organization of every human chromosome in diploid lymphoblasts
and primary fibroblasts. Most gene-rich chromosomes were concentrated at
the center of the nucleus, whereas the more gene-poor chromosomes were
located towards the nuclear periphery. There was no significant
relationship between chromosome size and position within the nucleus.
The intranuclear organization of chromosomes from an individual with
X-linked EDMD was not altered in cells lacking the nuclear membrane
protein emerin. The authors suggested that emerin may not be necessary
for localizing chromosomes at the nuclear periphery, and that the
muscular dystrophy phenotype in such individuals may not be due to
grossly altered nuclear organization of chromatin.

Zhang et al. (2007) identified mutations in the SYNE1 and SYNE2 genes in
patients with EDMD4 and EDMD5. Skin fibroblasts from these patients
showed similar defects in nuclear morphology as those described in
patients with EDMD due to mutations in the LMNA and EMD genes. SYNE1 and
SYNE2 mutant fibroblasts showed a convoluted appearance with
micronuclei, giant, and fragmented nuclei, and chromatin reorganization.
Patient fibroblasts and muscle cells showed loss of nuclear envelope
integrity with mislocalization of LMNA and emerin. Immunofluorescent
studies showed loss of SYNE1 or SYNE2 expression in the nuclear envelope
and mitochondria of patient fibroblasts. These same changes were also
observed in fibroblasts from patients with other genetic forms of EDMD,
indicating that loss of nesprin is a characteristic of all forms of
EDMD. RNA interference of SYNE1 or SYNE2 recapitulated the nuclear
defects membrane defects and changes in the organization of intranuclear
heterochromatin observed in patient cells. Overall, the findings showed
the importance of the nesprin/emerin/lamin complex in the maintenance of
nuclear stability, and suggested that changes in the binding
stoichiometry of these proteins is a common feature of EDMD. Zhang et
al. (2007) concluded that the disorder is caused in part by uncoupling
of the nucleoskeleton and cytoskeleton.

MAPPING

Consistent with the suggested linkage of EDMD with deutan colorblindness
(303800; Thomas et al., 1972), Boswinkel et al. (1985) reported possible
linkage between EDMD and DXS15, which is located at Xq28 (2 recombinants
out of 16 informative meioses). Thomas et al. (1986) found close linkage
with factor VIII and with DXS15 in a large family reported in detail by
Hopkins et al. (1981). Yates et al. (1986) found no recombination in 11
phase-known meioses informative for the factor VIII gene and 8
phase-known meioses informative for DXS15, giving maximum lod scores of
3.50 and 2.50, respectively, at a recombination fraction of 0. DXS52
(St14) showed 1 recombinant in 12 phase-known meioses, giving a maximum
lod score of 2.62 at a recombination fraction of 0.07. Hodgson et al.
(1986) found evidence of linkage to markers located at Xq28, thus
supporting the observations of others on the location of this form of
muscular dystrophy.

Romeo et al. (1988) concluded that the EDMD locus is probably located
distal to DXS15; the sum of lod scores from this study and from 2
previous ones was 6.31 at theta = 0.10. In 2 families living in northern
Georgia and Alabama, previously described by Waters et al. (1975),
Wright and Elsas (1980), and Hopkins et al. (1981), Consalez et al.
(1991) found that EDMD is approximately 2 cM from DXS52 (lod = 15.67)
and very close to F8C and the red/green color vision loci (see 300821),
with respective lod scores of 9.62 and 10.77, without a recombinant.
Several instances of recombination between EDMD and 3 proximal Xq28
markers suggested that the gene is located in distal Xq28, probably
distal to DXS305. Yates et al. (1993) concluded from a multipoint
analysis incorporating published data as well as their own that EDMD and
red-green cone pigments (which lie close to each other) are flanked
proximally by DXS52 (interval = 2 cM) and distally by F8C (interval = 3
cM).

MOLECULAR GENETICS

Among the many genes located in the distal part of Xq28, Bione et al.
(1994) selected 8 transcripts expressed at high levels in skeletal
muscle, heart, and/or brain as the best candidates for the site of the
mutation causing EDMD. On further study, they found that each of the 5
patients investigated had a unique mutation in one of the genes,
previously symbolized STA; see 300384.0001-300384.0005. These mutations
resulted in the loss of all or part of the protein.

Wulff et al. (1997) designed a set of primers optimized to amplify and
sequence each of the 6 EMD exons. With a heteroduplex analysis of emerin
gene exons in 30 unrelated EDMD patients, abnormal patterns of single
exons were found in 7 patients. Direct sequencing of the respective
exons revealed 6 novel mutations distributed in the promoter region and
exons 3-6. This study identified the first mutations in the promoter
region and in exon 5. With the mutations here described, a total of 25
mutations were then known. All of the mutations abolished the synthesis
of functional emerin.

GENOTYPE/PHENOTYPE CORRELATIONS

Ellis et al. (1999) stated that more than 70 different mutations causing
EDMD had been identified in the emerin gene. They described 2 missense
mutations involving proline-183 (300384.0008-300384.0009). Biochemical
analyses had demonstrated that the mobility and expression levels of the
mutant forms of emerin are indistinguishable from those of wildtype
emerin, but that they have weakened interactions with nuclear lamina
components. In comparison with the usual EDMD phenotype, patients with
P183 missense mutations had a later age at onset of first symptoms,
elbow contractures, ankle contractures, and upper and lower limb
weakness, but there was no difference for the age at onset of cardiac
involvement.

In 2 brothers with EDMD, Hoeltzenbein et al. (1999) identified a TCTAC
deletion spanning nucleotides 631-635 of the emerin gene (310300.0010).
Both showed an unusually severe disease phenotype. The same mutation had
been found in 2 brothers with a significantly milder phenotype from an
unrelated family (Manilal et al., 1998). The interfamilial heterogeneity
in the 2 families was thought to be due to environmental or genetic
modification of the disease.

Ben Yaou et al. (2007) reported a large consanguineous Algerian family
with digenic inheritance of mutations in the EMD and LMNA genes. Of 9
living affected family members, 6 (3 males and 3 females) had isolated
atrial cardiac disease with conduction abnormalities, 1 female had
isolated Charcot-Marie-Tooth axonal sensory neuropathy (CMT2B1; 605588),
and 2 males had severe Emery-Dreifuss muscular dystrophy, cardiac
disease, and CMT. Transmission of the atrial cardiac disease in this
family was consistent with X-linked inheritance, and all 6 patients with
isolated atrial cardiac disease had a deletion in the EMD gene. All 3
patients with CMT2B1 had a homozygous LMNA mutation (R298C;
150330.0020). The 2 male patients with all 3 phenotypes had both the
homozygous LMNA mutation and the EMD deletion. Heterozygous carriers of
the LMNA mutation had no associated phenotype. Three affected males
carrying the hemizygous EMD deletion, including 1 without and 2 with a
heterozygous LMNA mutation, did not have features of muscular dystrophy.
A fourth male patient carrying the EMD deletion and without the LMNA
mutation was asymptomatic; however, the 3 males with isolated atrial
cardiac disease were all over 40 years of age, and the fourth male was
32 years of age. Ben Yaou et al. (2007) concluded that the EMD deletion
acted in a dominant fashion and could alone cause isolated atrial
cardiac disease in both men and women, but not a complete EDMD phenotype
in men. Coexistence of the homozygous LMNA mutation and the hemizygous
EMD deletion in men both worsened the cardiac impairment and caused
axonal neuropathy and muscular dystrophy, suggesting a synergistic
effect of the 2 mutations.

*FIELD* SA
Bione et al. (1995); Cammann et al. (1974); Goebel et al. (1977);
Hassan et al. (1979); Hodgson et al. (1986); Klauck et al. (1995);
Petty et al. (1986); Rhead et al. (1978); Seay et al. (1977); Topaloglu
et al. (1994); Yamada and Kobayashi (1996); Yates et al. (1999); Yorifuji
et al. (1997)
*FIELD* RF
1. Becker, P. E.: Neues zur Genetik und Klassifikation der Muskeldystrophien. Humangenetik 17:
1-22, 1972.

2. Ben Yaou, R.; Toutain, A.; Arimura, T.; Demay, L.; Massart, C.;
Peccate, C.; Muchir, A.; Llense, S.; Deburgreave, N.; Leturcq, F.;
Litim, K. E.; Rahmoun-Chiali, N.; Richard, P.; Babuty, D.; Recan-Budiartha,
D.; Bonne, G.: Multitissular involvement in a family with LMNA and
EMD mutations: role of digenic mechanism? Neurology 68: 1883-1894,
2007.

3. Bione, S.; Maestrini, E.; Rivella, S.; Mancini, M.; Regis, S.;
Romeo, G.; Toniolo, D.: Identification of a novel X-linked gene responsible
for Emery-Dreifuss muscular dystrophy. Nature Genet. 8: 323-327,
1994.

4. Bione, S.; Small, K.; Aksmanovic, V. M. A.; D'Urso, M.; Ciccodicola,
A.; Merlini, L.; Morandi, L.; Kress, W.; Yates, J. R. W.; Warren,
S. T.; Toniolo, D.: Identification of new mutations in the Emery-Dreifuss
muscular dystrophy gene and evidence for genetic heterogeneity of
the disease. Hum. Molec. Genet. 4: 1859-1863, 1995.

5. Boswinkel, E.; Walker, A.; Hodgson, S.; Benham, F.; Bobrow, M.;
Davies, K.; Dubowitz, V.; Grenata, C.: Linkage analysis using eight
DNA polymorphisms along the length of the X chromosome locates the
gene for Emery-Dreyfuss muscular dystrophy to distal Xq. (Abstract) Cytogenet.
Cell Genet. 40: 586 only, 1985.

6. Boyle, S.; Gilchrist, S.; Bridger, J. M.; Mahy, N. L.; Ellis, J.
A.; Bickmore, W. A.: The spatial organization of human chromosomes
within the nuclei of normal and emerin-mutant cells. Hum. Molec.
Genet. 10: 211-219, 2001.

7. Buckley, A. E.; Dean, J.; Mahy, I. R.: Cardiac involvement in
Emery Dreifuss muscular dystrophy: a case series. Heart 82: 105-108,
1999.

8. Cammann, R.; Vehreschild, T.; Ernst, K.: Eine neue Sippe von X-chromosomaler
benigner Muskeldystrophie mit Fruhkontrakturen (Emery-Dreifuss). Psychiat.
Neurol. Med. Psychol. 26: 431-438, 1974.

9. Cartegni, L.; Raffaele di Barletta, M.; Barresi, R.; Squarzoni,
S.; Sabatelli, P.; Maraldi, N.; Mora, M.; Di Blasi, C.; Cornelio,
F.; Merlini, L.; Villa, A.; Cobianchi, F.; Toniolo, D.: Heart-specific
localization of emerin: new insights into Emery-Dreifuss muscular
dystrophy. Hum. Molec. Genet. 6: 2257-2264, 1997.

10. Cestan, R.; LeJonne, (NI).: Une myopathie avec retractions familiales. Nouv.
Iconogr. Salpetr. 15: 38-52, 1902.

11. Consalez, G. G.; Thomas, N. S. T.; Stayton, C. L.; Knight, S.
J. L.; Johnson, M.; Hopkins, L. C.; Harper, P. S.; Elsas, L. J.; Warren,
S. T.: Assignment of Emery-Dreifuss muscular dystrophy to the distal
region of Xq28: the results of a collaborative study. Am. J. Hum.
Genet. 48: 468-480, 1991.

12. Davidenkow, S.: Scapuloperoneal amyotrophy. Arch. Neurol. Psychiat. 41:
694-701, 1939.

13. Dickey, R. P.; Ziter, F. A.; Smith, R. A.: Emery-Dreifuss muscular
dystrophy. J. Pediat. 104: 555-559, 1984.

14. Dreifuss, F. E.; Hogan, G. R.: Survival in X-chromosomal muscular
dystrophy. Neurology 11: 734-737, 1961.

15. Dubowitz, V.: Rigid spine syndrome: a muscle syndrome in search
of a name. Proc. Roy. Soc. Med. 66: 219-220, 1973.

16. Ellis, J. A.; Yates, J. R. W.; Kendrick-Jones, J.; Brown, C. A.
: Changes at P183 of emerin weaken its protein-protein interactions
resulting in X-linked Emery-Dreifuss muscular dystrophy. Hum. Genet. 104:
262-268, 1999.

17. Emery, A. E. H.: Emery-Dreifuss syndrome. J. Med. Genet. 26:
637-641, 1989.

18. Emery, A. E. H.: X-linked muscular dystrophy with early contractures
and cardiomyopathy (Emery-Dreifuss type). Clin. Genet. 32: 360-367,
1987.

19. Emery, A. E. H.; Dreifuss, F. E.: Unusual type of benign X-linked
muscular dystrophy. J. Neurol. Neurosurg. Psychiat. 29: 338-342,
1966.

20. Fujimoto, S.; Ishikawa, T.; Saito, M.; Wada, Y.; Wada, I.; Arahata,
K.; Nonaka, I.: Early onset of X-linked Emery-Dreifuss muscular dystrophy
in a boy with emerin gene deletion. Neuropediatrics 30: 161-163,
1999.

21. Goebel, H. H.; Lenard, H. G.; Gorke, W.; Kunze, K.: Fibre type
disproportion in the rigid spine syndrome. Neuropaediatrie 8: 467-477,
1977.

22. Goldblatt, J.; Schram, L. J.; Wallis, G.; Oswald, A.; Beighton,
P.: Emery-Dreifuss syndrome and X-linked muscular dystrophy with
contractures: evidence for homogeneity. Clin. Genet. 35: 1-4, 1989.

23. Hassan, Z.; Fastabend, C. P.; Mohanty, P. K.; Isaacs, E. R.:
Atrioventricular block and supraventricular arrhythmias with X-linked
muscular dystrophy. Circulation 60: 1365-1369, 1979.

24. Hodgson, S.; Boswinkel, E.; Cole, C.; Walker, A.; Dubowitz, V.;
Granata, C.; Merlini, L.; Bobrow, M.: A linkage study of Emery-Dreifuss
muscular dystrophy. Hum. Genet. 74: 409-416, 1986.

25. Hodgson, S. V.; Boswinkel, E.; Walker, A.; Bobrow, M.; Davies,
K.; Dubowitz, V.; Granata, G.; Merlini, L.: Linkage analysis using
nine DNA polymorphisms along the length of the X chromosome locates
the gene for Emery-Dreifuss muscular dystrophy to distal Xq. (Abstract) J.
Med. Genet. 23: 169-170, 1986.

26. Hoeltzenbein, M.; Karow, T.; Zeller, J. A.; Warzok, R.; Wulff,
K.; Zschiesche, M.; Herrmann, F. H.; Grosse-Heitmeyer, W.; Wehnert,
M. S.: Severe clinical expression in X-linked Emery-Dreifuss muscular
dystrophy. Neuromusc. Disord. 9: 166-170, 1999.

27. Hopkins, L. C.; Jackson, J. A.; Elsas, L. J.: Emery-Dreifuss
humeroperoneal muscular dystrophy: an X-linked myopathy with unusual
contractures and bradycardia. Ann. Neurol. 10: 230-237, 1981.

28. Klauck, S.; Wilgenbus, P.; Yates, J. R. W.; Muller, C. R.; Poustka,
A.: Identification of novel mutations in three families with Emery-Dreifuss
muscular dystrophy. Hum. Molec. Genet. 4: 1853-1857, 1995.

29. Manilal, S.; Nguyen thi Man; Sewry, C. A.; Morris, G. E.: The
Emery-Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane
protein. Hum. Molec. Genet. 5: 801-808, 1996.

30. Manilal, S.; Recan, D.; Sewry, C. A.; Hoeltzenbein, M.; Llense,
S.; Leturcq, F.; Deburgrave, N.; Barbot, J.-C.; Nguyen thi Man; Muntoni,
F.; Wehnert, M.; Kaplan, J.-C.; Morris, G. E.: Mutations in Emery-Dreifuss
muscular dystrophy and their effects on emerin protein expression. Hum.
Molec. Genet. 7: 855-864, 1998.

31. Manilal, S.; Sewry, C. A.; Pereboev, A.; Man, N.; Gobbi, P.; Hawkes,
S.; Love, D. R.; Morris, G. E.: Distribution of emerin and lamins
in the heart and implications for Emery-Dreifuss muscular dystrophy. Hum.
Molec. Genet. 8: 353-359, 1999.

32. Mawatari, S.; Katayama, K.: Scapulo-peroneal muscular atrophy
with cardiopathy, an X-linked recessive trait. Arch. Neurol. 28:
55-59, 1973.

33. Merlini, L.; Granata, C.; Dominici, P.; Bonfiglioli, S.: Emery-Dreifuss
muscular dystrophy: report of five cases in a family and review of
the literature. Muscle Nerve 9: 481-485, 1986.

34. Nagano, A.; Koga, R.; Ogawa, M.; Kurano, Y.; Kawada, J.; Okada,
R.; Hayashi, Y. K.; Tsukahara, T.; Arahata, K.: Emerin deficiency
at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy. Nature
Genet. 12: 254-259, 1996.

35. Nevo, Y.; Al-Lozi, M.; Parsadanian, A. S.; Elliott, J. L.; Connolly,
A. M.; Pestronk, A.: Mutation analysis in Emery-Dreifuss muscular
dystrophy. Pediat. Neurol. 21: 456-459, 1999.

36. Pearson, C. M.; Kar, N. C.; Peter, J. B.; Munsat, T. L.: Muscle
lactate dehydrogenase patterns in two types of X-linked muscular dystrophy. Am.
J. Med. 39: 91-97, 1965.

37. Petty, R. K. H.; Thomas, P. K.; Landon, D. N.: Emery-Dreifuss
syndrome. J. Neurol. 233: 108-114, 1986.

38. Rhead, W.; Alexander, J.; Duckrow, B.; Batsford, W.; Rosenberg,
L. E.: X-linked neuromuscular syndrome with life-threatening atrioventricular
block. (Abstract) Am. J. Hum. Genet. 30: 64A only, 1978.

39. Romeo, G.; Roncuzzi, L.; Sangiorgi, S.; Giacanelli, M.; Liguori,
M.; Tessarolo, D.; Rocchi, M.: Mapping of the Emery-Dreifuss gene
through reconstruction of crossover points in two Italian pedigrees. Hum.
Genet. 80: 59-62, 1988.

40. Rotthauwe, H. W.; Mortier, W.; Beyer, H.: Neuer Typ einer recessiv
X-chromosomal vererbten Muskeldystrophie: scapulo-humero-distale Muskeldystrophie
mit fruehzeitigen Kontrakturen und Herzrhythmusstorungen. Humangenetik 16:
181-200, 1972.

41. Rowland, L. P.; Fetell, M.; Olarte, M.; Hays, A.; Singh, N.; Wanat,
F. E.: Emery-Dreifuss muscular dystrophy. Ann. Neurol. 5: 111-117,
1979.

42. Rudenskaya, G. E.; Ginter, E. K.; Petrin, A. N.; Djomina, N. A.
: Emery-Dreifuss syndrome: genetic and clinical varieties. Am. J.
Med. Genet. 50: 228-233, 1994.

43. Seay, A. R.; Ziter, F. A.; Petajan, J. H.: Rigid spine syndrome:
a type I fiber myopathy. Arch. Neurol. 34: 119-122, 1977.

44. Skinner, R.; Emery, A. E. H.: Serum creatine kinase levels in
carriers of Becker muscular dystrophy. (Letter) Lancet 304: 1023-1024,
1974. Note: Originally Volume II.

45. Sulaiman, A. R.; McQuillen, M. P.; Viste, K. M., Jr.; Hughes,
C. V.: Scapuloperoneal syndrome: report on two families with neurogenic
muscular atrophy. J. Neurol. Sci. 52: 305-325, 1981.

46. Takahashi, K.: Neurogenic scapuloperoneal amyotrophy associated
with dystrophic changes. Clin. Neurol. 11: 650-658, 1971.

47. Thomas, N. S. T.; Williams, H.; Elsas, L. J.; Hopkins, L. C.;
Sarfarazi, M.; Harper, P. S.: Localisation of the gene for Emery-Dreifuss
muscular dystrophy to the distal long arm of the X chromosome. J.
Med. Genet. 23: 596-598, 1986.

48. Thomas, P. K.; Calne, D. B.; Elliott, C. F.: X-linked scapuloperoneal
syndrome. J. Neurol. Neurosurg. Psychiat. 35: 208-215, 1972.

49. Thomas, P. K.; Petty, R. K. H.: Emery-Dreifuss muscular dystrophy.
(Abstract) J. Med. Genet. 22: 138-139, 1985.

50. Topaloglu, H.; Gogus, S.; Yalaz, K.; Kucukali, T.; Serdaroglu,
A.: Two siblings with nemaline myopathy presenting with rigid spine
syndrome. Neuromusc. Disord. 4: 263-267, 1994.

51. Ura, S.; Hayashi, Y. K.; Goto, K.; Astejada, M. N.; Murakami,
T.; Nagato, M.; Ohta, S.; Daimon, Y.; Takekawa, H.; Hirata, K.; Nonaka,
I.; Noguchi, S.; Nishino, I.: Limb-girdle muscular dystrophy due
to emerin gene mutations. Arch. Neurol. 64: 1038-1041, 2007.

52. Waters, D. D.; Nutter, D. O.; Hopkins, L. C.; Dorney, E. R.:
Cardiac features of an unusual X-linked humeroperoneal neuromuscular
disease. New Eng. J. Med. 293: 1017-1022, 1975.

53. Wettstein, A.; Hirth, H. R.; Janzer, R. C.; Jerusalem, F.; Steinmann,
B.: Rigid spine-syndrom. Verh. Dtsch. Ges. Neurol. 2: 812-814,
1983.

54. Wright, M. L.; Elsas, L. J., II.: Application of benefit-to-cost
analysis of an X-linked recessive cardiac and humeroperoneal neuromuscular
disease. Am. J. Med. Genet. 6: 315-329, 1980.

55. Wulff, K.; Parrish, J. E.; Herrmann, F. H.; Wehnert, M.: Six
novel mutations in the emerin gene causing X-linked Emery-Dreifuss
muscular dystrophy. Hum. Mutat. 9: 526-530, 1997.

56. Yamada, T.; Kobayashi, T.: A novel emerin mutation in a Japanese
patient with Emery-Dreifuss muscular dystrophy. Hum. Genet. 97:
693-694, 1996.

57. Yates, J. R. W.; Affara, N. A.; Jamieson, D. M.; Ferguson-Smith,
M. A.; Hausmanowa-Petrusewicz, I.; Zaremba, J.; Borkowska, J.; Johnston,
A. W.; Kelly, K.: Emery-Dreifuss muscular dystrophy: localisation
to Xq27.3-qter confirmed by linkage to the factor VIII gene. J. Med.
Genet. 23: 587-590, 1986.

58. Yates, J. R. W.; Bagshaw, J.; Aksmanovic, V. M. A.; Coomber, E.;
McMahon, R.; Whittaker, J. L.; Morrison, P. J.; Kendrick-Jones, J.;
Ellis, J. A.: Genotype-phenotype analysis in X-linked Emery-Dreifuss
muscular dystrophy and identification of a missense mutation associated
with a milder phenotype. Neuromusc. Disord. 9: 159-165, 1999.

59. Yates, J. R. W.; Warner, J. P.; Smith, J. A.; Deymeer, F.; Azulay,
J.-P.; Hausmanowa-Petrusewicz, I.; Zaremba, J.; Borkowska, J.; Affara,
N. A.; Ferguson-Smith, M. A.: Emery-Dreifuss muscular dystrophy:
linkage to markers in distal Xq28. J. Med. Genet. 30: 108-111, 1993.

60. Yorifuji, H.; Tadano, Y.; Tsuchiya, Y.; Ogawa, M.; Goto, K.; Umetani,
A.; Asaka, Y.; Arahata, K.: Emerin, deficiency of which causes Emery-Dreifuss
muscular dystrophy, is localized at the inner nuclear membrane. Neurogenetics 1:
135-140, 1997.

61. Zhang, Q.; Bethmann, C.; Worth, N. F.; Davies, J. D.; Wasner,
C.; Feuer, A.; Ragnauth, C. D.; Yi, Q.; Mellad, J. A.; Warren, D.
T.; Wheeler, M. A.; Ellis, J. A.; Skepper, J. N.; Vorgerd, M.; Schlotter-Weigel,
B.; Weissberg, P. L.; Roberts, R. G.; Wehnert, M.; Shanahan, C. M.
: Nesprin-1 and -2 are involved in the pathogenesis of Emery-Dreifuss
muscular dystrophy and are critical for nuclear envelope integrity. Hum.
Molec. Genet. 16: 2816-2833, 2007.

*FIELD* CS
INHERITANCE:
X-linked recessive

HEAD AND NECK:
[Neck];
Contracture of post-cervical muscles

CARDIOVASCULAR:
[Heart];
Cardiac conduction defects;
Atrial arrhythmias;
Atrioventricular block

CHEST:
[External features];
Mild pectus excavatum

SKELETAL:
[Limbs];
Contractures of the elbows;
[Feet];
Contractures of the Achilles tendon

MUSCLE, SOFT TISSUE:
Slowly-progressive muscle wasting and weakness with humeroperoneal
and scapuloperoneal distribution;
Absence of muscle pseudohypertrophy

NEUROLOGIC:
[Central nervous system];
Waddling gait;
Tendency to walk on toes

LABORATORY ABNORMALITIES:
Atrial abnormalities on electrocardiogram;
Myopathy with type I fiber atrophy on muscle biopsy;
Absence of emerin by immunohistochemistry on muscle biopsy;
Increased serum creatine kinase

MISCELLANEOUS:
Onset in childhood;
Adult onset has been rarely reported;
Risk of sudden death due to cardiac defects;
Female carriers may have cardiac defects

MOLECULAR BASIS:
Caused by mutation in the emerin gene (EMD, 300384.0001)

*FIELD* CN
Cassandra L. Kniffin - revised: 5/7/2002

*FIELD* CD
John F. Jackson: 6/15/1995

*FIELD* ED
joanna: 12/16/2013
joanna: 7/2/2013
ckniffin: 4/3/2008
ckniffin: 2/19/2008
alopez: 11/23/2004
ckniffin: 5/7/2002

*FIELD* CN
Cassandra L. Kniffin - updated: 9/2/2009
Cassandra L. Kniffin - updated: 4/3/2008
Cassandra L. Kniffin - updated: 1/30/2008
Cassandra L. Kniffin - reorganized: 4/2/2002
George E. Tiller - updated: 4/17/2001
Wilson H. Y. Lo - updated: 2/1/2000
Wilson H. Y. Lo - updated: 10/14/1999
Wilson H. Y. Lo - updated: 10/13/1999
Victor A. McKusick - updated: 10/5/1999
Victor A. McKusick - updated: 9/29/1999
Victor A. McKusick - updated: 4/26/1999
Victor A. McKusick - updated: 3/8/1999
Victor A. McKusick - updated: 5/5/1998
Victor A. McKusick - updated: 12/19/1997
Victor A. McKusick - updated: 6/26/1997
Victor A. McKusick - updated: 6/23/1997
Moyra Smith - updated: 6/22/1996

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
carol: 03/18/2013
ckniffin: 3/13/2013
alopez: 4/12/2011
carol: 4/8/2011
carol: 3/21/2011
carol: 9/14/2010
carol: 3/29/2010
carol: 1/6/2010
wwang: 10/9/2009
ckniffin: 10/5/2009
wwang: 9/9/2009
ckniffin: 9/2/2009
terry: 3/31/2009
wwang: 4/15/2008
ckniffin: 4/3/2008
wwang: 2/1/2008
ckniffin: 1/30/2008
ckniffin: 3/31/2005
ckniffin: 8/2/2004
carol: 4/30/2004
ckniffin: 4/29/2004
ckniffin: 4/2/2002
carol: 4/2/2002
ckniffin: 3/29/2002
carol: 3/13/2002
cwells: 4/26/2001
cwells: 4/17/2001
terry: 3/21/2001
carol: 2/28/2000
carol: 2/1/2000
terry: 2/1/2000
carol: 10/14/1999
carol: 10/13/1999
terry: 10/5/1999
terry: 9/29/1999
mgross: 5/7/1999
mgross: 4/29/1999
terry: 4/26/1999
carol: 3/25/1999
terry: 3/8/1999
mgross: 2/24/1999
mgross: 2/18/1999
terry: 2/17/1999
alopez: 7/2/1998
terry: 6/23/1998
carol: 5/12/1998
terry: 5/5/1998
dholmes: 1/23/1998
mark: 1/5/1998
terry: 12/19/1997
jenny: 7/1/1997
terry: 6/26/1997
jenny: 6/23/1997
terry: 7/2/1996
carol: 6/22/1996
mark: 4/16/1996
terry: 4/9/1996
mark: 3/25/1996
mark: 3/14/1996
terry: 2/29/1996
mark: 1/5/1996
mark: 1/4/1996
pfoster: 7/6/1995
mark: 6/11/1995
carol: 2/3/1995
mimadm: 5/17/1994
warfield: 4/20/1994
carol: 3/18/1993

RBCC Red Blood Cell Collection

Full text data of EMD