Full text data of COLQ
COLQ
[Confidence: low (only semi-automatic identification from reviews)]
Acetylcholinesterase collagenic tail peptide (AChE Q subunit; Acetylcholinesterase-associated collagen; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Acetylcholinesterase collagenic tail peptide (AChE Q subunit; Acetylcholinesterase-associated collagen; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y215
ID COLQ_HUMAN Reviewed; 455 AA.
AC Q9Y215; B3KY09; Q6DK18; Q6YH18; Q6YH19; Q6YH20; Q6YH21; Q9NP18;
read moreAC Q9NP19; Q9NP20; Q9NP21; Q9NP22; Q9NP23; Q9NP24; Q9UP88;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Acetylcholinesterase collagenic tail peptide;
DE AltName: Full=AChE Q subunit;
DE AltName: Full=Acetylcholinesterase-associated collagen;
DE Flags: Precursor;
GN Name=COLQ;
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], AND VARIANT CMSE SER-430.
RC TISSUE=Blood, and Skeletal muscle;
RX PubMed=9758617; DOI=10.1086/302059;
RA Donger C., Krejci E., Serradell A.P., Eymard B., Bon S., Nicole S.,
RA Chateau D., Gary F., Fardeau M., Massoulie J., Guicheney P.;
RT "Mutation in the human acetylcholinesterase-associated collagen gene,
RT COLQ, is responsible for congenital myasthenic syndrome with end-plate
RT acetylcholinesterase deficiency (Type Ic).";
RL Am. J. Hum. Genet. 63:967-975(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Skeletal muscle;
RX PubMed=9689136; DOI=10.1073/pnas.95.16.9654;
RA Ohno K., Brengman J., Tsujino A., Engel A.G.;
RT "Human endplate acetylcholinesterase deficiency caused by mutations in
RT the collagen-like tail subunit (ColQ) of the asymmetric enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9654-9659(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Arredondo J., DeLeon M.;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM II).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 53-67 IN COMPLEX WITH ACHE.
RX PubMed=15526038; DOI=10.1038/sj.emboj.7600425;
RA Dvir H., Harel M., Bon S., Liu W.-Q., Vidal M., Garbay C.,
RA Sussman J.L., Massoulie J., Silman I.;
RT "The synaptic acetylcholinesterase tetramer assembles around a
RT polyproline II helix.";
RL EMBO J. 23:4394-4405(2004).
RN [9]
RP VARIANTS CMSE GLN-59; GLU-342; GLN-410 AND TYR-444.
RC TISSUE=Blood, and Muscle;
RX PubMed=10665486;
RX DOI=10.1002/1531-8249(200002)47:2<162::AID-ANA5>3.3.CO;2-H;
RA Ohno K., Engel A.G., Brengman J.M., Shen X.-M., Heidenreich F.,
RA Vincent A., Milone M., Tan E., Demirci M., Walsh P., Nakano S.,
RA Akiguchi I.;
RT "The spectrum of mutations causing end-plate acetylcholinesterase
RT deficiency.";
RL Ann. Neurol. 47:162-170(2000).
CC -!- FUNCTION: Anchors the catalytic subunits of asymmetric AChE to the
CC synaptic basal lamina.
CC -!- SUBUNIT: Homotrimer. Component of the asymmetric form of AChE, a
CC disulfide-bonded oligomer composed of the collagenic subunits (Q)
CC and a variable number of asymmetric catalytic subunits (T). The N-
CC terminal of a collagenic subunit (Q) associates with the C-
CC terminal of a catalytic subunit (T).
CC -!- INTERACTION:
CC P22303:ACHE; NbExp=2; IntAct=EBI-1637847, EBI-1637793;
CC -!- SUBCELLULAR LOCATION: Cell junction, synapse.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=I;
CC IsoId=Q9Y215-1; Sequence=Displayed;
CC Name=II;
CC IsoId=Q9Y215-2; Sequence=VSP_001175;
CC Name=III;
CC IsoId=Q9Y215-3; Sequence=VSP_001177;
CC Name=IV;
CC IsoId=Q9Y215-4; Sequence=VSP_001176;
CC Name=V;
CC IsoId=Q9Y215-5; Sequence=VSP_001178;
CC Name=VI;
CC IsoId=Q9Y215-6; Sequence=VSP_001179, VSP_001183;
CC Name=VII;
CC IsoId=Q9Y215-7; Sequence=VSP_001180, VSP_001182;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=VIII;
CC IsoId=Q9Y215-8; Sequence=VSP_001181, VSP_001184;
CC -!- TISSUE SPECIFICITY: Found at the end plate of skeletal muscle.
CC -!- DOMAIN: The proline-rich attachment domain (PRAD) binds the AChE
CC catalytic subunits.
CC -!- PTM: The triple-helical tail is stabilized by disulfide bonds at
CC each end.
CC -!- DISEASE: Myasthenic syndrome, congenital, Engel type (CMSE)
CC [MIM:603034]: A rare autosomal recessive congenital myasthenic
CC syndrome characterized by onset during childhood, generalized
CC weakness, abnormal fatigability on exertion, refrectoriness to
CC acetylcholinesterase drugs, decremental electromyographic response
CC and morphological abnormalities of the neuromuscular junctions.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the COLQ family.
CC -!- SIMILARITY: Contains 2 collagen-like domains.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/COLQ";
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DR EMBL; AJ225895; CAA12648.1; -; mRNA.
DR EMBL; AF057036; AAC39927.1; -; mRNA.
DR EMBL; AF229126; AAF43195.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43196.1; -; Genomic_DNA.
DR EMBL; AF229118; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43197.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43198.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43199.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43200.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43201.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43202.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AY150334; AAO06814.1; -; mRNA.
DR EMBL; AY150336; AAO06816.1; -; mRNA.
DR EMBL; AY150337; AAO06817.1; -; mRNA.
DR EMBL; AY150338; AAO06818.1; -; mRNA.
DR EMBL; AY150339; AAO06819.1; -; mRNA.
DR EMBL; AK128401; BAG54671.1; -; mRNA.
DR EMBL; CH471055; EAW64250.1; -; Genomic_DNA.
DR EMBL; BC074828; AAH74828.1; -; mRNA.
DR EMBL; BC074829; AAH74829.1; -; mRNA.
DR RefSeq; NP_005668.2; NM_005677.3.
DR RefSeq; NP_536799.1; NM_080538.2.
DR RefSeq; NP_536800.2; NM_080539.3.
DR RefSeq; XP_005265559.1; XM_005265502.1.
DR RefSeq; XP_005265560.1; XM_005265503.1.
DR RefSeq; XP_005265561.1; XM_005265504.1.
DR UniGene; Hs.146735; -.
DR PDB; 1VZJ; X-ray; 2.35 A; I/J=53-67.
DR PDBsum; 1VZJ; -.
DR ProteinModelPortal; Q9Y215; -.
DR IntAct; Q9Y215; 1.
DR PhosphoSite; Q9Y215; -.
DR DMDM; 116241309; -.
DR PaxDb; Q9Y215; -.
DR PRIDE; Q9Y215; -.
DR Ensembl; ENST00000383781; ENSP00000373291; ENSG00000206561.
DR Ensembl; ENST00000383786; ENSP00000373296; ENSG00000206561.
DR Ensembl; ENST00000383787; ENSP00000373297; ENSG00000206561.
DR Ensembl; ENST00000383788; ENSP00000373298; ENSG00000206561.
DR Ensembl; ENST00000603808; ENSP00000474271; ENSG00000206561.
DR GeneID; 8292; -.
DR KEGG; hsa:8292; -.
DR UCSC; uc003bzx.3; human.
DR CTD; 8292; -.
DR GeneCards; GC03M015491; -.
DR HGNC; HGNC:2226; COLQ.
DR MIM; 603033; gene.
DR MIM; 603034; phenotype.
DR neXtProt; NX_Q9Y215; -.
DR Orphanet; 98915; Synaptic congenital myasthenic syndromes.
DR PharmGKB; PA26743; -.
DR eggNOG; NOG329823; -.
DR HOVERGEN; HBG102052; -.
DR InParanoid; Q9Y215; -.
DR EvolutionaryTrace; Q9Y215; -.
DR GeneWiki; COLQ; -.
DR GenomeRNAi; 8292; -.
DR NextBio; 31075; -.
DR PRO; PR:Q9Y215; -.
DR ArrayExpress; Q9Y215; -.
DR Bgee; Q9Y215; -.
DR Genevestigator; Q9Y215; -.
DR GO; GO:0005605; C:basal lamina; TAS:ProtInc.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0001507; P:acetylcholine catabolic process in synaptic cleft; TAS:ProtInc.
DR GO; GO:0008105; P:asymmetric protein localization; TAS:ProtInc.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR011936; Myxo_disulph_rpt.
DR Pfam; PF01391; Collagen; 1.
DR TIGRFAMs; TIGR02232; myxo_disulf_rpt; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Collagen;
KW Complete proteome; Congenital myasthenic syndrome; Disease mutation;
KW Disulfide bond; Neurotransmitter degradation; Polymorphism;
KW Reference proteome; Repeat; Signal; Synapse.
FT SIGNAL 1 22 Potential.
FT CHAIN 23 455 Acetylcholinesterase collagenic tail
FT peptide.
FT /FTId=PRO_0000005854.
FT DOMAIN 96 269 Collagen-like 1.
FT DOMAIN 277 291 Collagen-like 2.
FT REGION 51 67 PRAD.
FT REGION 130 133 Heparan sulfate proteoglycan binding
FT (Potential).
FT REGION 235 238 Heparan sulfate proteoglycan binding
FT (Potential).
FT DISULFID 51 51 Interchain (with T subunit) (Potential).
FT DISULFID 52 52 Interchain (with T subunit) (Potential).
FT DISULFID 93 93 Interchain (Potential).
FT DISULFID 291 291 Interchain (Potential).
FT DISULFID 293 293 Interchain (Potential).
FT VAR_SEQ 1 35 MVVLNPMTLGIYLQLFFLSIVSQPTFINSVLPISA -> MT
FT GSSFSLAHLLIISGLLCYSAGCL (in isoform II).
FT /FTId=VSP_001175.
FT VAR_SEQ 73 76 Missing (in isoform IV).
FT /FTId=VSP_001176.
FT VAR_SEQ 74 107 Missing (in isoform III).
FT /FTId=VSP_001177.
FT VAR_SEQ 124 132 Missing (in isoform V).
FT /FTId=VSP_001178.
FT VAR_SEQ 240 291 GQKGDSGVMGPPGKPGPSGQPGRPGPPGPPPAGQLIMGPKG
FT ERGFPGPPGRC -> SSRTPCTLPRRPPVPCGQGSRSPVTV
FT VAGNESQACLLPRFEEDYISSGTERG (in isoform
FT VI).
FT /FTId=VSP_001179.
FT VAR_SEQ 272 281 GQLIMGPKGE -> DFCGQQPGGA (in isoform
FT VII).
FT /FTId=VSP_001180.
FT VAR_SEQ 273 329 QLIMGPKGERGFPGPPGRCLCGPTMNVNNPSYGESVYGPSS
FT PRVPVIFVVNNQEELE -> HMETCNAPSTATSTPRPAATS
FT PEGREEKVGCAPQNWQQLLHCHQTGHVLAPSPPTFV (in
FT isoform VIII).
FT /FTId=VSP_001181.
FT VAR_SEQ 282 455 Missing (in isoform VII).
FT /FTId=VSP_001182.
FT VAR_SEQ 292 455 Missing (in isoform VI).
FT /FTId=VSP_001183.
FT VAR_SEQ 330 455 Missing (in isoform VIII).
FT /FTId=VSP_001184.
FT VARIANT 59 59 P -> Q (in CMSE; abrogates binding to T
FT subunit).
FT /FTId=VAR_010133.
FT VARIANT 312 312 S -> G (in dbSNP:rs6782980).
FT /FTId=VAR_048809.
FT VARIANT 342 342 D -> E (in CMSE; impairs anchoring to the
FT basal lamina).
FT /FTId=VAR_010134.
FT VARIANT 410 410 R -> Q (in CMSE).
FT /FTId=VAR_010135.
FT VARIANT 430 430 Y -> S (in CMSE).
FT /FTId=VAR_010136.
FT VARIANT 444 444 C -> Y (in CMSE).
FT /FTId=VAR_010137.
FT CONFLICT 370 370 D -> N (in Ref. 3; AAO06818).
FT CONFLICT 399 399 R -> RD (in Ref. 1; CAA12648 and 3;
FT AAO06814/AAO06816/AAO06817/AAO06818/
FT AAO06819).
FT CONFLICT 400 400 C -> Y (in Ref. 3; AAO06816).
FT CONFLICT 404 404 Y -> D (in Ref. 3; AAO06817).
FT CONFLICT 423 423 G -> V (in Ref. 3; AAO06819).
SQ SEQUENCE 455 AA; 47766 MW; A95D3E5D5ECDBE55 CRC64;
MVVLNPMTLG IYLQLFFLSI VSQPTFINSV LPISAALPSL DQKKRGGHKA CCLLTPPPPP
LFPPPFFRGG RSPLLSPDMK NLMLELETSQ SPCMQGSLGS PGPPGPQGPP GLPGKTGPKG
EKGELGRPGR KGRPGPPGVP GMPGPIGWPG PEGPRGEKGD LGMMGLPGSR GPMGSKGYPG
SRGEKGSRGE KGDLGPKGEK GFPGFPGMLG QKGEMGPKGE PGIAGHRGPT GRPGKRGKQG
QKGDSGVMGP PGKPGPSGQP GRPGPPGPPP AGQLIMGPKG ERGFPGPPGR CLCGPTMNVN
NPSYGESVYG PSSPRVPVIF VVNNQEELER LNTQNAIAFR RDQRSLYFKD SLGWLPIQLT
PFYPVDYTAD QHGTCGDGLL QPGEECDDGN SDVGDDCIRC HRAYCGDGHR HEGVEDCDGS
DFGYLTCETY LPGSYGDLQC TQYCYIDSTP CRYFT
//
ID COLQ_HUMAN Reviewed; 455 AA.
AC Q9Y215; B3KY09; Q6DK18; Q6YH18; Q6YH19; Q6YH20; Q6YH21; Q9NP18;
read moreAC Q9NP19; Q9NP20; Q9NP21; Q9NP22; Q9NP23; Q9NP24; Q9UP88;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Acetylcholinesterase collagenic tail peptide;
DE AltName: Full=AChE Q subunit;
DE AltName: Full=Acetylcholinesterase-associated collagen;
DE Flags: Precursor;
GN Name=COLQ;
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], AND VARIANT CMSE SER-430.
RC TISSUE=Blood, and Skeletal muscle;
RX PubMed=9758617; DOI=10.1086/302059;
RA Donger C., Krejci E., Serradell A.P., Eymard B., Bon S., Nicole S.,
RA Chateau D., Gary F., Fardeau M., Massoulie J., Guicheney P.;
RT "Mutation in the human acetylcholinesterase-associated collagen gene,
RT COLQ, is responsible for congenital myasthenic syndrome with end-plate
RT acetylcholinesterase deficiency (Type Ic).";
RL Am. J. Hum. Genet. 63:967-975(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Skeletal muscle;
RX PubMed=9689136; DOI=10.1073/pnas.95.16.9654;
RA Ohno K., Brengman J., Tsujino A., Engel A.G.;
RT "Human endplate acetylcholinesterase deficiency caused by mutations in
RT the collagen-like tail subunit (ColQ) of the asymmetric enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9654-9659(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Arredondo J., DeLeon M.;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM II).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 53-67 IN COMPLEX WITH ACHE.
RX PubMed=15526038; DOI=10.1038/sj.emboj.7600425;
RA Dvir H., Harel M., Bon S., Liu W.-Q., Vidal M., Garbay C.,
RA Sussman J.L., Massoulie J., Silman I.;
RT "The synaptic acetylcholinesterase tetramer assembles around a
RT polyproline II helix.";
RL EMBO J. 23:4394-4405(2004).
RN [9]
RP VARIANTS CMSE GLN-59; GLU-342; GLN-410 AND TYR-444.
RC TISSUE=Blood, and Muscle;
RX PubMed=10665486;
RX DOI=10.1002/1531-8249(200002)47:2<162::AID-ANA5>3.3.CO;2-H;
RA Ohno K., Engel A.G., Brengman J.M., Shen X.-M., Heidenreich F.,
RA Vincent A., Milone M., Tan E., Demirci M., Walsh P., Nakano S.,
RA Akiguchi I.;
RT "The spectrum of mutations causing end-plate acetylcholinesterase
RT deficiency.";
RL Ann. Neurol. 47:162-170(2000).
CC -!- FUNCTION: Anchors the catalytic subunits of asymmetric AChE to the
CC synaptic basal lamina.
CC -!- SUBUNIT: Homotrimer. Component of the asymmetric form of AChE, a
CC disulfide-bonded oligomer composed of the collagenic subunits (Q)
CC and a variable number of asymmetric catalytic subunits (T). The N-
CC terminal of a collagenic subunit (Q) associates with the C-
CC terminal of a catalytic subunit (T).
CC -!- INTERACTION:
CC P22303:ACHE; NbExp=2; IntAct=EBI-1637847, EBI-1637793;
CC -!- SUBCELLULAR LOCATION: Cell junction, synapse.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=I;
CC IsoId=Q9Y215-1; Sequence=Displayed;
CC Name=II;
CC IsoId=Q9Y215-2; Sequence=VSP_001175;
CC Name=III;
CC IsoId=Q9Y215-3; Sequence=VSP_001177;
CC Name=IV;
CC IsoId=Q9Y215-4; Sequence=VSP_001176;
CC Name=V;
CC IsoId=Q9Y215-5; Sequence=VSP_001178;
CC Name=VI;
CC IsoId=Q9Y215-6; Sequence=VSP_001179, VSP_001183;
CC Name=VII;
CC IsoId=Q9Y215-7; Sequence=VSP_001180, VSP_001182;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=VIII;
CC IsoId=Q9Y215-8; Sequence=VSP_001181, VSP_001184;
CC -!- TISSUE SPECIFICITY: Found at the end plate of skeletal muscle.
CC -!- DOMAIN: The proline-rich attachment domain (PRAD) binds the AChE
CC catalytic subunits.
CC -!- PTM: The triple-helical tail is stabilized by disulfide bonds at
CC each end.
CC -!- DISEASE: Myasthenic syndrome, congenital, Engel type (CMSE)
CC [MIM:603034]: A rare autosomal recessive congenital myasthenic
CC syndrome characterized by onset during childhood, generalized
CC weakness, abnormal fatigability on exertion, refrectoriness to
CC acetylcholinesterase drugs, decremental electromyographic response
CC and morphological abnormalities of the neuromuscular junctions.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the COLQ family.
CC -!- SIMILARITY: Contains 2 collagen-like domains.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/COLQ";
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DR EMBL; AJ225895; CAA12648.1; -; mRNA.
DR EMBL; AF057036; AAC39927.1; -; mRNA.
DR EMBL; AF229126; AAF43195.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43195.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43196.1; -; Genomic_DNA.
DR EMBL; AF229118; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43196.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43197.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43197.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43198.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43198.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43199.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229123; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229125; AAF43199.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43200.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43200.1; JOINED; Genomic_DNA.
DR EMBL; AF229124; AAF43201.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43201.1; JOINED; Genomic_DNA.
DR EMBL; AF229126; AAF43202.1; -; Genomic_DNA.
DR EMBL; AF229117; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229118; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229119; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229120; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229121; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AF229122; AAF43202.1; JOINED; Genomic_DNA.
DR EMBL; AY150334; AAO06814.1; -; mRNA.
DR EMBL; AY150336; AAO06816.1; -; mRNA.
DR EMBL; AY150337; AAO06817.1; -; mRNA.
DR EMBL; AY150338; AAO06818.1; -; mRNA.
DR EMBL; AY150339; AAO06819.1; -; mRNA.
DR EMBL; AK128401; BAG54671.1; -; mRNA.
DR EMBL; CH471055; EAW64250.1; -; Genomic_DNA.
DR EMBL; BC074828; AAH74828.1; -; mRNA.
DR EMBL; BC074829; AAH74829.1; -; mRNA.
DR RefSeq; NP_005668.2; NM_005677.3.
DR RefSeq; NP_536799.1; NM_080538.2.
DR RefSeq; NP_536800.2; NM_080539.3.
DR RefSeq; XP_005265559.1; XM_005265502.1.
DR RefSeq; XP_005265560.1; XM_005265503.1.
DR RefSeq; XP_005265561.1; XM_005265504.1.
DR UniGene; Hs.146735; -.
DR PDB; 1VZJ; X-ray; 2.35 A; I/J=53-67.
DR PDBsum; 1VZJ; -.
DR ProteinModelPortal; Q9Y215; -.
DR IntAct; Q9Y215; 1.
DR PhosphoSite; Q9Y215; -.
DR DMDM; 116241309; -.
DR PaxDb; Q9Y215; -.
DR PRIDE; Q9Y215; -.
DR Ensembl; ENST00000383781; ENSP00000373291; ENSG00000206561.
DR Ensembl; ENST00000383786; ENSP00000373296; ENSG00000206561.
DR Ensembl; ENST00000383787; ENSP00000373297; ENSG00000206561.
DR Ensembl; ENST00000383788; ENSP00000373298; ENSG00000206561.
DR Ensembl; ENST00000603808; ENSP00000474271; ENSG00000206561.
DR GeneID; 8292; -.
DR KEGG; hsa:8292; -.
DR UCSC; uc003bzx.3; human.
DR CTD; 8292; -.
DR GeneCards; GC03M015491; -.
DR HGNC; HGNC:2226; COLQ.
DR MIM; 603033; gene.
DR MIM; 603034; phenotype.
DR neXtProt; NX_Q9Y215; -.
DR Orphanet; 98915; Synaptic congenital myasthenic syndromes.
DR PharmGKB; PA26743; -.
DR eggNOG; NOG329823; -.
DR HOVERGEN; HBG102052; -.
DR InParanoid; Q9Y215; -.
DR EvolutionaryTrace; Q9Y215; -.
DR GeneWiki; COLQ; -.
DR GenomeRNAi; 8292; -.
DR NextBio; 31075; -.
DR PRO; PR:Q9Y215; -.
DR ArrayExpress; Q9Y215; -.
DR Bgee; Q9Y215; -.
DR Genevestigator; Q9Y215; -.
DR GO; GO:0005605; C:basal lamina; TAS:ProtInc.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0001507; P:acetylcholine catabolic process in synaptic cleft; TAS:ProtInc.
DR GO; GO:0008105; P:asymmetric protein localization; TAS:ProtInc.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR011936; Myxo_disulph_rpt.
DR Pfam; PF01391; Collagen; 1.
DR TIGRFAMs; TIGR02232; myxo_disulf_rpt; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Collagen;
KW Complete proteome; Congenital myasthenic syndrome; Disease mutation;
KW Disulfide bond; Neurotransmitter degradation; Polymorphism;
KW Reference proteome; Repeat; Signal; Synapse.
FT SIGNAL 1 22 Potential.
FT CHAIN 23 455 Acetylcholinesterase collagenic tail
FT peptide.
FT /FTId=PRO_0000005854.
FT DOMAIN 96 269 Collagen-like 1.
FT DOMAIN 277 291 Collagen-like 2.
FT REGION 51 67 PRAD.
FT REGION 130 133 Heparan sulfate proteoglycan binding
FT (Potential).
FT REGION 235 238 Heparan sulfate proteoglycan binding
FT (Potential).
FT DISULFID 51 51 Interchain (with T subunit) (Potential).
FT DISULFID 52 52 Interchain (with T subunit) (Potential).
FT DISULFID 93 93 Interchain (Potential).
FT DISULFID 291 291 Interchain (Potential).
FT DISULFID 293 293 Interchain (Potential).
FT VAR_SEQ 1 35 MVVLNPMTLGIYLQLFFLSIVSQPTFINSVLPISA -> MT
FT GSSFSLAHLLIISGLLCYSAGCL (in isoform II).
FT /FTId=VSP_001175.
FT VAR_SEQ 73 76 Missing (in isoform IV).
FT /FTId=VSP_001176.
FT VAR_SEQ 74 107 Missing (in isoform III).
FT /FTId=VSP_001177.
FT VAR_SEQ 124 132 Missing (in isoform V).
FT /FTId=VSP_001178.
FT VAR_SEQ 240 291 GQKGDSGVMGPPGKPGPSGQPGRPGPPGPPPAGQLIMGPKG
FT ERGFPGPPGRC -> SSRTPCTLPRRPPVPCGQGSRSPVTV
FT VAGNESQACLLPRFEEDYISSGTERG (in isoform
FT VI).
FT /FTId=VSP_001179.
FT VAR_SEQ 272 281 GQLIMGPKGE -> DFCGQQPGGA (in isoform
FT VII).
FT /FTId=VSP_001180.
FT VAR_SEQ 273 329 QLIMGPKGERGFPGPPGRCLCGPTMNVNNPSYGESVYGPSS
FT PRVPVIFVVNNQEELE -> HMETCNAPSTATSTPRPAATS
FT PEGREEKVGCAPQNWQQLLHCHQTGHVLAPSPPTFV (in
FT isoform VIII).
FT /FTId=VSP_001181.
FT VAR_SEQ 282 455 Missing (in isoform VII).
FT /FTId=VSP_001182.
FT VAR_SEQ 292 455 Missing (in isoform VI).
FT /FTId=VSP_001183.
FT VAR_SEQ 330 455 Missing (in isoform VIII).
FT /FTId=VSP_001184.
FT VARIANT 59 59 P -> Q (in CMSE; abrogates binding to T
FT subunit).
FT /FTId=VAR_010133.
FT VARIANT 312 312 S -> G (in dbSNP:rs6782980).
FT /FTId=VAR_048809.
FT VARIANT 342 342 D -> E (in CMSE; impairs anchoring to the
FT basal lamina).
FT /FTId=VAR_010134.
FT VARIANT 410 410 R -> Q (in CMSE).
FT /FTId=VAR_010135.
FT VARIANT 430 430 Y -> S (in CMSE).
FT /FTId=VAR_010136.
FT VARIANT 444 444 C -> Y (in CMSE).
FT /FTId=VAR_010137.
FT CONFLICT 370 370 D -> N (in Ref. 3; AAO06818).
FT CONFLICT 399 399 R -> RD (in Ref. 1; CAA12648 and 3;
FT AAO06814/AAO06816/AAO06817/AAO06818/
FT AAO06819).
FT CONFLICT 400 400 C -> Y (in Ref. 3; AAO06816).
FT CONFLICT 404 404 Y -> D (in Ref. 3; AAO06817).
FT CONFLICT 423 423 G -> V (in Ref. 3; AAO06819).
SQ SEQUENCE 455 AA; 47766 MW; A95D3E5D5ECDBE55 CRC64;
MVVLNPMTLG IYLQLFFLSI VSQPTFINSV LPISAALPSL DQKKRGGHKA CCLLTPPPPP
LFPPPFFRGG RSPLLSPDMK NLMLELETSQ SPCMQGSLGS PGPPGPQGPP GLPGKTGPKG
EKGELGRPGR KGRPGPPGVP GMPGPIGWPG PEGPRGEKGD LGMMGLPGSR GPMGSKGYPG
SRGEKGSRGE KGDLGPKGEK GFPGFPGMLG QKGEMGPKGE PGIAGHRGPT GRPGKRGKQG
QKGDSGVMGP PGKPGPSGQP GRPGPPGPPP AGQLIMGPKG ERGFPGPPGR CLCGPTMNVN
NPSYGESVYG PSSPRVPVIF VVNNQEELER LNTQNAIAFR RDQRSLYFKD SLGWLPIQLT
PFYPVDYTAD QHGTCGDGLL QPGEECDDGN SDVGDDCIRC HRAYCGDGHR HEGVEDCDGS
DFGYLTCETY LPGSYGDLQC TQYCYIDSTP CRYFT
//
MIM
603033
*RECORD*
*FIELD* NO
603033
*FIELD* TI
*603033 COLLAGENIC TAIL OF ENDPLATE ACETYLCHOLINESTERASE; COLQ
;;ACETYLCHOLINESTERASE-ASSOCIATED COLLAGEN
read more*FIELD* TX
DESCRIPTION
The COLQ gene encodes a collagen-like strand that associates into a
triple helix to form a tail that anchors catalytic subunits of
acetylcholinesterase (ACHE; 100740) to the basal lamina.
Asymmetric AChE is the major form of AChE at the endplate of the
neuromuscular junction in higher vertebrates. Asymmetric AChE is
composed of the T isoform of ACHE, ACHE(T), linked to a triple helical
COLQ tail. AChE rapidly hydrolyzes acetylcholine released at cholinergic
synapses in the nervous system, thus limiting the number of collisions
between ACh and the ACh receptor (AChR), and the duration of the
synaptic response (Ohno et al., 1998).
CLONING
Krejci et al. (1991) cloned ColQ from Torpedo. Krejci et al. (1997)
cloned the rat and mouse ColQ genes, and found that the ColQ subunits
form homotrimers and attach to AChE. Northern blot analysis detected
ColQ expression in cholinergic tissues, brain, muscle, and heart, as
well as in noncholinergic tissues such as lung and testes.
Ohno et al. (1998) used mouse ColQ primers to isolate human COLQ cDNA
from a human adult skeletal muscle cDNA library. The cDNA encodes a
deduced 455-amino acid protein with 89% homology to the rodent ColQ
peptide. Conserved domains include a secretion signal peptide, a
proline-rich attachment domain (PRAD) that interacts with AChE(T), 2
cysteines that form disulfide bonds with AChE(T), a collagen domain,
conserved cysteines that stabilize the tripal helical domain, and
proteoglycan binding domains that anchor the tripal helical domain to
the basal lamina. Several alternative transcripts were identified.
GENE STRUCTURE
Ohno et al. (1998) determined that the COLQ gene spans approximately 50
kb and comprises 17 constitutive exons and 2 alternatively transcribed
exons.
MAPPING
By fluorescence in situ hybridization, Ohno et al. (1998) mapped the
COLQ gene to chromosome 3p25. By radiation hybrid analysis, Donger et
al. (1998) mapped the COLQ gene to chromosome 3p24.2.
MOLECULAR GENETICS
In patients with endplate AChE deficiency (EAD; 603034), Ohno et al.
(1998) identified 6 recessive mutations in the COLQ gene
(603033.0001-603033.0006). Coexpression of each of the 6 ColQ mutants
with wildtype AChE(T) in SV40-transformed monkey kidney fibroblast (COS)
cells showed that a mutation proximal to the ColQ attachment domain for
AChE(T) prevented association of ColQ with AChE(T); mutations distal to
the attachment domain generated a mutant species of acetylcholinesterase
composed of 1 AChE(T) tetramer and a truncated ColQ strand. The authors
concluded that the mutations prevented the insertion of the gene product
into the basal lamina.
In 6 sibs with a mild form of endplate AChE deficiency, Donger et al.
(1998) identified a homozygous mutation in the COLQ gene (603033.0007).
Shapira et al. (2002) reported 3 novel mutations in the COLQ gene in 8
patients with variable features of EAD: 1 patient was a compound
heterozygote; the other 7 patients, 6 Palestinian Arabs and 1 Iraqi Jew,
were all homozygous for a gly240-to-ter mutation (G240X; 603033.0010),
suggesting a founder mutation. Expression studies of the 3 mutations in
COS-7 cells showed that each prevented formation of insertion competent
asymmetric AChE.
ANIMAL MODEL
Feng et al. (1999) generated ColQ -/- mice to study the roles played by
ColQ and AChE in synapses and elsewhere. Such mice failed to thrive and
most died before reaching maturity. They completely lacked asymmetric
AChE in skeletal and cardiac muscles, specifically at the neuromuscular
junction and in the brain. Nonetheless, neuromuscular function was
present. A compensatory mechanism appeared to be a partial ensheathment
of nerve terminals by Schwann cells. Such mice also lacked the
asymmetric forms of Bche (177400). Surprisingly, globular AChE tetramers
were absent as well, suggesting a role for the ColQ gene in assembly or
stabilization of AChE forms that do not contain a collagenous subunit.
*FIELD* AV
.0001
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, 215-BP DEL, NT107
In a patient with endplate acetylcholinesterase deficiency (603034),
Ohno et al. (1998) found deletion of 215 basepairs following nucleotide
107 of the COLQ gene. The deletion was caused by skipping of exons 2 and
3, causing a frameshift after codon 35. The mutation abolished the
proline-rich attachment domain (PRAD) and predicted 25 missense codons
followed by a stop codon. The mutation was present in compound
heterozygous state with the E214X mutation (603033.0002). The deletion
mutation was inherited from the mother and the truncating mutation from
the father.
.0002
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, GLU214TER
See 603033.0001 and Ohno et al. (1998). In another patient with EAD
(603034), Ohno et al. (1998) identified homozygosity for the
glu214-to-ter (E214X) mutation.
.0003
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, SER169TER
In a patient with EAD (603034), Ohno et al. (1998) identified a
homozygous ser169-to-ter (S169X) mutation, which resulted in loss of the
distal two-thirds of the collagen domain.
.0004
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, ARG282TER
In a patient with EAD (603034), Ohno et al. (1998) identified compound
heterozygosity for 2 mutations in the COLQ gene: an arg282-to-ter
(R282X) mutation and a 1-bp deletion (1082delC). The R282X mutation
truncated COLQ 10 codons upstream to the C-terminal end of the collagen
domain. The 1-bp deletion caused a frameshift after codon 360,
predicting 64 missense codons followed by a stop codon; 1082delC spared
the entire collagen domain but abolished the C-terminal domain of COLQ.
.0005
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, 1-BP DEL, 1082C
See 603033.0005 and Ohno et al. (1998). In another patient with EAD
(603034), Ohno et al. (1998) identified homozygosity for the 1082delC
mutation. The asymptomatic parents were heterozygous for the mutation.
.0006
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, 1-BP INS, 788C
In a patient with EAD (603034), Ohno et al. (1998) identified a
homozygous 1-bp insertion (788insC) in the COLQ gene that caused a
frameshift after codon 262, predicting 36 missense codons followed by a
stop codon. The 788insC mutation spared 85% of the collagen domain. The
asymptomatic parents were heterozygous for the mutation.
.0007
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, TYR431SER
In 6 affected sibs in a consanguineous Spanish family with EAD (603034),
Donger et al. (1998) identified a homozygous tyr431-to-ser (Y431S)
substitution in the conserved C-terminal domain of COLQ. The mutation
was predicted to disturb the attachment of collagen-tailed
acetylcholinesterase to the neuromuscular junction. Donger et al. (1998)
referred to the disorder in these patients as CMS Ic (for congenital
myasthenic syndrome type Ic). The authors noted that most previously
described CMS Ic patients had a marked decrease in total muscle
acetylcholinesterase with essentially no collagen-tailed forms. These
forms were present in affected members of the Spanish family but the
defect interfered with attachment to the neuromuscular junction.
.0008
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, ARG315TER
Ohno et al. (1999) described a patient with congenital EAD (603034)
caused by compound heterozygosity for an arg315-to-ter (R315X) mutation
and a splice donor site mutation at position +3 of intron 16 of COLQ
(603033.0009).
.0009
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, IVS16DS, A-G, +3
See 603033.0008 and Ohno et al. (1999). Using a minigene harboring the
COLQ IVS16+3A-G mutation for functional expression studies, Ohno et al.
(1999) found that the splice site mutation resulted in skipping of exon
16. The mutant splice donor site of intron 16 harbors 5 discordant
nucleotides (at -3, -2, +3, +4, and +6) that do not basepair with U1
small nuclear (sn) RNA (RNU1; 180680), the RNA responsible for splice
donor site recognition. Versions of the minigene harboring, at either +4
or +6, nucleotides complementary to U1 snRNA restored normal splicing.
Analysis of 1,801 native splice donor sites revealed that the presence
of a G nucleotide at +3 is associated with preferential usage, at
positions +4 to +6, of nucleotides concordant to U1 snRNA. Analysis of
11 disease-associated IVS+3A-G mutations indicated that, on average, 2
of 3 nucleotides at positions +4 to +6 failed to basepair, and that the
nucleotide at +4 never basepaired, with U1 snRNA. Ohno et al. (1999)
concluded that, with G at +3, normal splicing generally depends on the
concordance that residues at +4 to +6 have with U1 snRNA, but other
cis-acting elements may also be important in assuring the fidelity of
splicing.
.0010
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, GLY240TER
In 6 Palestinian Arabs and 1 Iraqi Jew with variable features of EAD
(603034), Shapira et al. (2002) identified a homozygous 718G-T
transition in a splice acceptor consensus sequence of exon 12 of the
COLQ gene, resulting in a gly240-to-ter (G240X) mutation and causing
premature termination of the protein. The mutation prevented proper
formation of asymmetric AChE in COS-7 cells. The patients demonstrated
phenotypic variability, including differences in age of onset, disease
progression, respiratory and feeding difficulties, severity of weakness,
and ophthalmoplegia.
*FIELD* SA
Engel et al. (1977)
*FIELD* RF
1. Donger, C.; Krejci, E.; Serradell, A. P.; Eymard, B.; Bon, S.;
Nicole, S.; Chateau, D.; Gary, F.; Fardeau, M.; Massoulie, J.; Guicheney,
P.: Mutation in the human acetylcholinesterase-associated collagen
gene, COLQ, is responsible for congenital myasthenic syndrome with
end-plate acetylcholinesterase deficiency (type Ic). Am. J. Hum.
Genet. 63: 967-975, 1998.
2. Engel, A. G.; Lambert, E. H.; Gomez, M. R.: A new myasthenic syndrome
with end-plate acetylcholinesterase deficiency, small nerve terminals,
and reduced acetylcholine release. Ann. Neurol. 1: 315-330, 1977.
3. Feng, G.; Krejci, E.; Molgo, J.; Cunningham, J. M.; Massoulie,
J.; Sanes, J. R.: Genetic analysis of collagen Q: roles in acetylcholinesterase
and butyrylcholinesterase assembly and in synaptic structure and function. J.
Cell Biol. 144: 1349-1360, 1999.
4. Krejci, E.; Coussen, F.; Duval, N.; Chatel, J.-M.; Legay, C.; Puype,
M.; Vandekerckhove, J.; Cartaud, J.; Bon, S.; Massoulie, J.: Primary
structure of a collagenic tail peptide of torpedo acetylcholinesterase:
co-expression with catalytic subunit induces the production of collagen-tailed
forms in transfected cells. EMBO J. 10: 1285-1293, 1991.
5. Krejci, E.; Thomine, S.; Boschetti, N.; Legay, C.; Sketelj, J.;
Massoulie, J.: The mammalian gene of acetylcholinesterase-associated
collagen. J. Biol. Chem. 272: 22840-22847, 1997.
6. Ohno, K.; Brengman, J.; Tsujino, A.; Engel, A. G.: Human endplate
acetylcholinesterase deficiency caused by mutations in the collagen-like
tail subunit (ColQ) of the asymmetric enzyme. Proc. Nat. Acad. Sci. 95:
9654-9659, 1998.
7. Ohno, K.; Brengman, J. M.; Felice, K. J.; Cornblath, D. R.; Engel,
A. G.: Congenital end-plate acetylcholinesterase deficiency caused
by a nonsense mutation and an A-to-G splice-donor-site mutation at
position +3 of the collagenlike-tail-subunit gene (COLQ): how does
G at position +3 result in aberrant splicing? Am. J. Hum. Genet. 65:
635-644, 1999.
8. Shapira, Y. A.; Sadeh, M. E.; Bergtraum, M. P.; Tsujino, A.; Ohno,
K.; Shen, X.-M.; Brengman, J.; Edwardson, S.; Matoth, I.; Engel, A.
G.: Three novel COLQ mutations and variation of phenotypic expressivity
due to G240X. Neurology 58: 603-609, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/3/2003
Victor A. McKusick - updated: 9/20/1999
Wilson H. Y. Lo - updated: 7/26/1999
Victor A. McKusick - updated: 10/22/1998
*FIELD* CD
Victor A. McKusick: 9/14/1998
*FIELD* ED
carol: 09/30/2013
carol: 10/7/2004
ckniffin: 9/29/2004
carol: 1/3/2003
tkritzer: 12/23/2002
ckniffin: 12/18/2002
jlewis: 9/30/1999
terry: 9/20/1999
carol: 7/26/1999
carol: 10/26/1998
terry: 10/22/1998
dkim: 9/21/1998
carol: 9/15/1998
carol: 9/14/1998
*RECORD*
*FIELD* NO
603033
*FIELD* TI
*603033 COLLAGENIC TAIL OF ENDPLATE ACETYLCHOLINESTERASE; COLQ
;;ACETYLCHOLINESTERASE-ASSOCIATED COLLAGEN
read more*FIELD* TX
DESCRIPTION
The COLQ gene encodes a collagen-like strand that associates into a
triple helix to form a tail that anchors catalytic subunits of
acetylcholinesterase (ACHE; 100740) to the basal lamina.
Asymmetric AChE is the major form of AChE at the endplate of the
neuromuscular junction in higher vertebrates. Asymmetric AChE is
composed of the T isoform of ACHE, ACHE(T), linked to a triple helical
COLQ tail. AChE rapidly hydrolyzes acetylcholine released at cholinergic
synapses in the nervous system, thus limiting the number of collisions
between ACh and the ACh receptor (AChR), and the duration of the
synaptic response (Ohno et al., 1998).
CLONING
Krejci et al. (1991) cloned ColQ from Torpedo. Krejci et al. (1997)
cloned the rat and mouse ColQ genes, and found that the ColQ subunits
form homotrimers and attach to AChE. Northern blot analysis detected
ColQ expression in cholinergic tissues, brain, muscle, and heart, as
well as in noncholinergic tissues such as lung and testes.
Ohno et al. (1998) used mouse ColQ primers to isolate human COLQ cDNA
from a human adult skeletal muscle cDNA library. The cDNA encodes a
deduced 455-amino acid protein with 89% homology to the rodent ColQ
peptide. Conserved domains include a secretion signal peptide, a
proline-rich attachment domain (PRAD) that interacts with AChE(T), 2
cysteines that form disulfide bonds with AChE(T), a collagen domain,
conserved cysteines that stabilize the tripal helical domain, and
proteoglycan binding domains that anchor the tripal helical domain to
the basal lamina. Several alternative transcripts were identified.
GENE STRUCTURE
Ohno et al. (1998) determined that the COLQ gene spans approximately 50
kb and comprises 17 constitutive exons and 2 alternatively transcribed
exons.
MAPPING
By fluorescence in situ hybridization, Ohno et al. (1998) mapped the
COLQ gene to chromosome 3p25. By radiation hybrid analysis, Donger et
al. (1998) mapped the COLQ gene to chromosome 3p24.2.
MOLECULAR GENETICS
In patients with endplate AChE deficiency (EAD; 603034), Ohno et al.
(1998) identified 6 recessive mutations in the COLQ gene
(603033.0001-603033.0006). Coexpression of each of the 6 ColQ mutants
with wildtype AChE(T) in SV40-transformed monkey kidney fibroblast (COS)
cells showed that a mutation proximal to the ColQ attachment domain for
AChE(T) prevented association of ColQ with AChE(T); mutations distal to
the attachment domain generated a mutant species of acetylcholinesterase
composed of 1 AChE(T) tetramer and a truncated ColQ strand. The authors
concluded that the mutations prevented the insertion of the gene product
into the basal lamina.
In 6 sibs with a mild form of endplate AChE deficiency, Donger et al.
(1998) identified a homozygous mutation in the COLQ gene (603033.0007).
Shapira et al. (2002) reported 3 novel mutations in the COLQ gene in 8
patients with variable features of EAD: 1 patient was a compound
heterozygote; the other 7 patients, 6 Palestinian Arabs and 1 Iraqi Jew,
were all homozygous for a gly240-to-ter mutation (G240X; 603033.0010),
suggesting a founder mutation. Expression studies of the 3 mutations in
COS-7 cells showed that each prevented formation of insertion competent
asymmetric AChE.
ANIMAL MODEL
Feng et al. (1999) generated ColQ -/- mice to study the roles played by
ColQ and AChE in synapses and elsewhere. Such mice failed to thrive and
most died before reaching maturity. They completely lacked asymmetric
AChE in skeletal and cardiac muscles, specifically at the neuromuscular
junction and in the brain. Nonetheless, neuromuscular function was
present. A compensatory mechanism appeared to be a partial ensheathment
of nerve terminals by Schwann cells. Such mice also lacked the
asymmetric forms of Bche (177400). Surprisingly, globular AChE tetramers
were absent as well, suggesting a role for the ColQ gene in assembly or
stabilization of AChE forms that do not contain a collagenous subunit.
*FIELD* AV
.0001
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, 215-BP DEL, NT107
In a patient with endplate acetylcholinesterase deficiency (603034),
Ohno et al. (1998) found deletion of 215 basepairs following nucleotide
107 of the COLQ gene. The deletion was caused by skipping of exons 2 and
3, causing a frameshift after codon 35. The mutation abolished the
proline-rich attachment domain (PRAD) and predicted 25 missense codons
followed by a stop codon. The mutation was present in compound
heterozygous state with the E214X mutation (603033.0002). The deletion
mutation was inherited from the mother and the truncating mutation from
the father.
.0002
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, GLU214TER
See 603033.0001 and Ohno et al. (1998). In another patient with EAD
(603034), Ohno et al. (1998) identified homozygosity for the
glu214-to-ter (E214X) mutation.
.0003
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, SER169TER
In a patient with EAD (603034), Ohno et al. (1998) identified a
homozygous ser169-to-ter (S169X) mutation, which resulted in loss of the
distal two-thirds of the collagen domain.
.0004
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, ARG282TER
In a patient with EAD (603034), Ohno et al. (1998) identified compound
heterozygosity for 2 mutations in the COLQ gene: an arg282-to-ter
(R282X) mutation and a 1-bp deletion (1082delC). The R282X mutation
truncated COLQ 10 codons upstream to the C-terminal end of the collagen
domain. The 1-bp deletion caused a frameshift after codon 360,
predicting 64 missense codons followed by a stop codon; 1082delC spared
the entire collagen domain but abolished the C-terminal domain of COLQ.
.0005
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, 1-BP DEL, 1082C
See 603033.0005 and Ohno et al. (1998). In another patient with EAD
(603034), Ohno et al. (1998) identified homozygosity for the 1082delC
mutation. The asymptomatic parents were heterozygous for the mutation.
.0006
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, 1-BP INS, 788C
In a patient with EAD (603034), Ohno et al. (1998) identified a
homozygous 1-bp insertion (788insC) in the COLQ gene that caused a
frameshift after codon 262, predicting 36 missense codons followed by a
stop codon. The 788insC mutation spared 85% of the collagen domain. The
asymptomatic parents were heterozygous for the mutation.
.0007
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, TYR431SER
In 6 affected sibs in a consanguineous Spanish family with EAD (603034),
Donger et al. (1998) identified a homozygous tyr431-to-ser (Y431S)
substitution in the conserved C-terminal domain of COLQ. The mutation
was predicted to disturb the attachment of collagen-tailed
acetylcholinesterase to the neuromuscular junction. Donger et al. (1998)
referred to the disorder in these patients as CMS Ic (for congenital
myasthenic syndrome type Ic). The authors noted that most previously
described CMS Ic patients had a marked decrease in total muscle
acetylcholinesterase with essentially no collagen-tailed forms. These
forms were present in affected members of the Spanish family but the
defect interfered with attachment to the neuromuscular junction.
.0008
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, ARG315TER
Ohno et al. (1999) described a patient with congenital EAD (603034)
caused by compound heterozygosity for an arg315-to-ter (R315X) mutation
and a splice donor site mutation at position +3 of intron 16 of COLQ
(603033.0009).
.0009
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, IVS16DS, A-G, +3
See 603033.0008 and Ohno et al. (1999). Using a minigene harboring the
COLQ IVS16+3A-G mutation for functional expression studies, Ohno et al.
(1999) found that the splice site mutation resulted in skipping of exon
16. The mutant splice donor site of intron 16 harbors 5 discordant
nucleotides (at -3, -2, +3, +4, and +6) that do not basepair with U1
small nuclear (sn) RNA (RNU1; 180680), the RNA responsible for splice
donor site recognition. Versions of the minigene harboring, at either +4
or +6, nucleotides complementary to U1 snRNA restored normal splicing.
Analysis of 1,801 native splice donor sites revealed that the presence
of a G nucleotide at +3 is associated with preferential usage, at
positions +4 to +6, of nucleotides concordant to U1 snRNA. Analysis of
11 disease-associated IVS+3A-G mutations indicated that, on average, 2
of 3 nucleotides at positions +4 to +6 failed to basepair, and that the
nucleotide at +4 never basepaired, with U1 snRNA. Ohno et al. (1999)
concluded that, with G at +3, normal splicing generally depends on the
concordance that residues at +4 to +6 have with U1 snRNA, but other
cis-acting elements may also be important in assuring the fidelity of
splicing.
.0010
ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY
COLQ, GLY240TER
In 6 Palestinian Arabs and 1 Iraqi Jew with variable features of EAD
(603034), Shapira et al. (2002) identified a homozygous 718G-T
transition in a splice acceptor consensus sequence of exon 12 of the
COLQ gene, resulting in a gly240-to-ter (G240X) mutation and causing
premature termination of the protein. The mutation prevented proper
formation of asymmetric AChE in COS-7 cells. The patients demonstrated
phenotypic variability, including differences in age of onset, disease
progression, respiratory and feeding difficulties, severity of weakness,
and ophthalmoplegia.
*FIELD* SA
Engel et al. (1977)
*FIELD* RF
1. Donger, C.; Krejci, E.; Serradell, A. P.; Eymard, B.; Bon, S.;
Nicole, S.; Chateau, D.; Gary, F.; Fardeau, M.; Massoulie, J.; Guicheney,
P.: Mutation in the human acetylcholinesterase-associated collagen
gene, COLQ, is responsible for congenital myasthenic syndrome with
end-plate acetylcholinesterase deficiency (type Ic). Am. J. Hum.
Genet. 63: 967-975, 1998.
2. Engel, A. G.; Lambert, E. H.; Gomez, M. R.: A new myasthenic syndrome
with end-plate acetylcholinesterase deficiency, small nerve terminals,
and reduced acetylcholine release. Ann. Neurol. 1: 315-330, 1977.
3. Feng, G.; Krejci, E.; Molgo, J.; Cunningham, J. M.; Massoulie,
J.; Sanes, J. R.: Genetic analysis of collagen Q: roles in acetylcholinesterase
and butyrylcholinesterase assembly and in synaptic structure and function. J.
Cell Biol. 144: 1349-1360, 1999.
4. Krejci, E.; Coussen, F.; Duval, N.; Chatel, J.-M.; Legay, C.; Puype,
M.; Vandekerckhove, J.; Cartaud, J.; Bon, S.; Massoulie, J.: Primary
structure of a collagenic tail peptide of torpedo acetylcholinesterase:
co-expression with catalytic subunit induces the production of collagen-tailed
forms in transfected cells. EMBO J. 10: 1285-1293, 1991.
5. Krejci, E.; Thomine, S.; Boschetti, N.; Legay, C.; Sketelj, J.;
Massoulie, J.: The mammalian gene of acetylcholinesterase-associated
collagen. J. Biol. Chem. 272: 22840-22847, 1997.
6. Ohno, K.; Brengman, J.; Tsujino, A.; Engel, A. G.: Human endplate
acetylcholinesterase deficiency caused by mutations in the collagen-like
tail subunit (ColQ) of the asymmetric enzyme. Proc. Nat. Acad. Sci. 95:
9654-9659, 1998.
7. Ohno, K.; Brengman, J. M.; Felice, K. J.; Cornblath, D. R.; Engel,
A. G.: Congenital end-plate acetylcholinesterase deficiency caused
by a nonsense mutation and an A-to-G splice-donor-site mutation at
position +3 of the collagenlike-tail-subunit gene (COLQ): how does
G at position +3 result in aberrant splicing? Am. J. Hum. Genet. 65:
635-644, 1999.
8. Shapira, Y. A.; Sadeh, M. E.; Bergtraum, M. P.; Tsujino, A.; Ohno,
K.; Shen, X.-M.; Brengman, J.; Edwardson, S.; Matoth, I.; Engel, A.
G.: Three novel COLQ mutations and variation of phenotypic expressivity
due to G240X. Neurology 58: 603-609, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/3/2003
Victor A. McKusick - updated: 9/20/1999
Wilson H. Y. Lo - updated: 7/26/1999
Victor A. McKusick - updated: 10/22/1998
*FIELD* CD
Victor A. McKusick: 9/14/1998
*FIELD* ED
carol: 09/30/2013
carol: 10/7/2004
ckniffin: 9/29/2004
carol: 1/3/2003
tkritzer: 12/23/2002
ckniffin: 12/18/2002
jlewis: 9/30/1999
terry: 9/20/1999
carol: 7/26/1999
carol: 10/26/1998
terry: 10/22/1998
dkim: 9/21/1998
carol: 9/15/1998
carol: 9/14/1998
MIM
603034
*RECORD*
*FIELD* NO
603034
*FIELD* TI
#603034 ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY; EAD
;;ENGEL CONGENITAL MYASTHENIC SYNDROME;;
read moreMYASTHENIC SYNDROME, CONGENITAL, ENGEL TYPE;;
CONGENITAL MYASTHENIC SYNDROME TYPE Ic; CMS1C;;
CMS Ic
*FIELD* TX
A number sign (#) is used with this entry because endplate
acetylcholinesterase deficiency is caused by mutation in the gene
encoding the collagenic tail of endplate acetylcholinesterase (AChE)
(COLQ; 603033).
DESCRIPTION
Congenital myasthenic syndromes (CMS) are genetic disorders of the
neuromuscular junction that can be classified by the site of the
transmission defect: presynaptic, synaptic, and postsynaptic. Endplate
AChE deficiency is an autosomal recessive congenital myasthenic syndrome
characterized by a defect within the synapse at the neuromuscular
junction.
For a discussion of genetic heterogeneity of CMS, see 608931.
CLINICAL FEATURES
Engel et al. (1977) reported a patient with a severely disabling CMS
associated with endplate acetylcholinesterase deficiency. Symptoms began
soon after birth with generalized weakness increased by exertion,
fatigability, hyporeflexia, and no response to AChE inhibitors. EMG
showed a decremental response to stimulation and a repetitive response
to single nerve stimulation. Miniature endplate potentials (MEPP) had
prolonged duration and decreased frequency. Electron microscopy of
muscle biopsy showed decreased nerve terminal size, reduced postsynaptic
membrane density, and focal degeneration of the postsynaptic folds.
Degenerating nuclei were also present. Histochemical analysis did not
detect AChE at the endplate. Engel et al. (1977) suggested a congenital
defect in the molecular assembly of AChE or its attachment to the
postsynaptic membrane.
Hutchinson et al. (1993) reported studies of the patient reported by
Engel et al. (1977) and 4 other patients, 2 of whom were sisters. All
patients had generalized weakness that was exacerbated by exertion, and
mild slowing of the pupillary light reflex; however, ophthalmoparesis
was not a constant feature. Electrophysiologic studies revealed a
decremental response to stimulation, prolonged endplate currents, and
reduced quantal release. All patients had absence of AChE from the
neuromuscular junction, which explained the lack of clinical benefit
from AChE inhibitors. Electron microscopy showed small nerve terminals,
abnormal encasement of the presynaptic membrane by Schwann cells, and
degeneration of the junctional folds and organelles in the junctional
sarcoplasm. Muscle extracts from 3 patients showed absence of the
collagen tail of AChE, while kinetic properties of the enzyme were
normal. Studies of the AChE catalytic subunit gene (ACHE; 100740)
revealed no abnormality in the exons that encode the domain to which the
tail subunit binds. Hutchinson et al. (1993) concluded that the
molecular defect resided in a faulty tail subunit, preventing assembly
of the AChE enzyme.
Jennekens et al. (1992) reported a 6-year-old boy with partial
deficiency of both endplate acetylcholinesterase and the
acetylcholinesterase receptor (see 608931).
In a study of 5 patients with congenital myasthenia associated with
endplate acetylcholinesterase deficiency, Camp et al. (1995) found that
the ACHE gene had a normal sequence and normal assembly of catalytic
subunits. The authors suggested that the defect resided in an altered
structure of the collagen-containing tail subunit or, alternatively, in
an alteration in a protein involved in promoting the assembly between
the catalytic subunit and tail unit.
Donger et al. (1998) reported a large consanguineous Spanish family in
which 6 of 11 sibs had CMS with endplate AChE deficiency. Age at onset
ranged from 6 to 10 years. By the second decade, all patients complained
of great fatigability on exertion. One of them presented with permanent
neck and upper limb weakness; another had generalized weakness.
Electrophysiologic studies performed on 4 patients showed impaired
muscle-nerve conduction, with decremental responses at 3 Hz, repetitive
responses to single motor nerve stimulation, and abnormal jitter. A
discrete ptosis, in the one who had generalized weakness, was indicative
of a mild myopathic syndrome. No anti-AChR antibody was detected.
Parenteral administration of anticholinesterase drugs had either no
benefit or worsening effect.
MOLECULAR GENETICS
In 6 patients with AChE deficiency, Ohno et al. (1998) identified 6
recessive mutations in the COLQ gene (603033.0001-603033.0006). Two of
the patients had previously been reported by Engel et al. (1977) and
Hutchinson et al. (1993).
In affected members of a consanguineous Spanish family with EAD, Donger
et al. (1998) identified a homozygous mutation in the COLQ gene
(603033.0007).
Shapira et al. (2002) reported 3 novel mutations in the COLQ gene in 8
patients with variable features of EAD: 1 patient was a compound
heterozygote; the other 7 patients, 6 Palestinian Arabs and 1 Iraqi Jew,
were all homozygous for a gly240-to-ter mutation (G240X; 603033.0010),
suggesting a founder effect. The patients with the G240X mutation
demonstrated phenotypic variability, including differences in age of
onset, disease progression, respiratory and feeding difficulties,
severity of weakness, and ophthalmoplegia.
*FIELD* SA
Greer and Schotland (1960)
*FIELD* RF
1. Camp, S.; Bon, S.; Li, Y.; Getman, D. K.; Engel, A. G.; Massoulie,
J.; Taylor, P.: Patients with congenital myasthenia associated with
end-plate acetylcholinesterase deficiency show normal sequence, mRNA
splicing, and assembly of catalytic subunits. J. Clin. Invest. 95:
333-340, 1995.
2. Donger, C.; Krejci, E.; Serradell, A. P.; Eymard, B.; Bon, S.;
Nicole, S.; Chateau, D.; Gary, F.; Fardeau, M.; Massoulie, J.; Guicheney,
P.: Mutation in the human acetylcholinesterase-associated collagen
gene, COLQ, is responsible for congenital myasthenic syndrome with
end-plate acetylcholinesterase deficiency (type Ic). Am. J. Hum.
Genet. 63: 967-975, 1998.
3. Engel, A. G.; Lambert, E. H.; Gomez, M. R.: A new myasthenic syndrome
with end-plate acetylcholinesterase deficiency, small nerve terminals,
and reduced acetylcholine release. Ann. Neurol. 1: 315-330, 1977.
4. Greer, M.; Schotland, M.: Myasthenia gravis in the newborn. Pediatrics 26:
101-108, 1960.
5. Hutchinson, D. O.; Walls, T. J.; Nakano, S.; Camp, S.; Taylor,
P.; Harper, C. M.; Groover, R. V.; Peterson, H. A.; Jamieson, D. G.;
Engel, A. G.: Congenital endplate acetylcholinesterase deficiency. Brain 116:
633-653, 1993.
6. Jennekens, F. G. I.; Hesselmans, L. F. G. M.; Veldman, H.; Jansen,
E. N. H.; Spaans, F.; Molenaar, P. C.: Deficiency of acetylcholine
receptors in a case of endplate acetylcholinesterase deficiency: a
histochemical investigation. Muscle Nerve 15: 63-72, 1992.
7. Ohno, K.; Brengman, J.; Tsujino, A.; Engel, A. G.: Human endplate
acetylcholinesterase deficiency caused by mutations in the collagen-like
tail subunit (ColQ) of the asymmetric enzyme. Proc. Nat. Acad. Sci. 95:
9654-9659, 1998.
8. Shapira, Y. A.; Sadeh, M. E.; Bergtraum, M. P.; Tsujino, A.; Ohno,
K.; Shen, X.-M.; Brengman, J.; Edwardson, S.; Matoth, I.; Engel, A.
G.: Three novel COLQ mutations and variation of phenotypic expressivity
due to G240X. Neurology 58: 603-609, 2002.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Ptosis;
Ophthalmoparesis;
Slow, delayed pupillary light reflex
RESPIRATORY:
Respiratory insufficiency due to muscle weakness
ABDOMEN:
[Gastrointestinal];
Poor feeding due to muscle weakness;
Dysphagia
SKELETAL:
[Spine];
Scoliosis;
Lordosis
MUSCLE, SOFT TISSUE:
Underdeveloped muscles;
Muscle biopsy shows type 2 fiber atrophy;
Muscle biopsy shows endplate myopathy (see details under NEUROLOGIC
heading)
NEUROLOGIC:
[Peripheral nervous system];
Generalized weakness due to defect at the neuromuscular junction;
Weakness is exacerbated by exertion;
Hypotonia;
Easy fatigability;
Limb weakness;
Dysarthria;
EMG shows decremental compound muscle action potential (CMAP) response
to repetitive nerve stimulation;
Multiple CMAP response to single nerve stimulation;
Prolonged miniature endplate potentials (MEPP);
Prolonged miniature endplate currents (MEPC);
Decreased frequency of MEPP;
Muscle biopsy shows absence of acetylcholinesterase (AChE) from neuromuscular
junction;
Muscle biopsy shows decreased size of nerve terminals;
Muscle biopsy shows decreased size of endplates;
Muscle biopsy shows decreased postsynaptic membrane density;
Muscle biopsy shows focal degeneration of postsynaptic junctional
folds;
Muscle biopsy shows abnormal encasement of presynaptic membrane by
Schwann cells
VOICE:
Weak cry
IMMUNOLOGY:
Absence of acetylcholine receptor (AChR) autoantibodies
MISCELLANEOUS:
Onset usually in infancy;
Later childhood onset has been reported;
Phenotypic variation in severity and symptoms;
No response or worsening with acetylcholinesterase inhibitors;
Symptoms progress with worsening myopathy
MOLECULAR BASIS:
Caused by mutation in the collagenic tail of endplate acetylcholinesterase
gene (COLQ, 603033.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/24/2004
*FIELD* ED
joanna: 10/11/2004
ckniffin: 9/29/2004
*FIELD* CN
Cassandra L. Kniffin - reorganized: 10/7/2004
Cassandra L. Kniffin - updated: 9/29/2004
Cassandra L. Kniffin - updated: 12/18/2002
Victor A. McKusick - updated: 10/22/1998
*FIELD* CD
Victor A. McKusick: 9/14/1998
*FIELD* ED
joanna: 10/13/2004
carol: 10/7/2004
ckniffin: 9/30/2004
ckniffin: 9/29/2004
carol: 1/3/2003
tkritzer: 12/23/2002
ckniffin: 12/18/2002
alopez: 4/15/2002
carol: 10/26/1998
terry: 10/22/1998
dkim: 9/21/1998
carol: 9/14/1998
*RECORD*
*FIELD* NO
603034
*FIELD* TI
#603034 ENDPLATE ACETYLCHOLINESTERASE DEFICIENCY; EAD
;;ENGEL CONGENITAL MYASTHENIC SYNDROME;;
read moreMYASTHENIC SYNDROME, CONGENITAL, ENGEL TYPE;;
CONGENITAL MYASTHENIC SYNDROME TYPE Ic; CMS1C;;
CMS Ic
*FIELD* TX
A number sign (#) is used with this entry because endplate
acetylcholinesterase deficiency is caused by mutation in the gene
encoding the collagenic tail of endplate acetylcholinesterase (AChE)
(COLQ; 603033).
DESCRIPTION
Congenital myasthenic syndromes (CMS) are genetic disorders of the
neuromuscular junction that can be classified by the site of the
transmission defect: presynaptic, synaptic, and postsynaptic. Endplate
AChE deficiency is an autosomal recessive congenital myasthenic syndrome
characterized by a defect within the synapse at the neuromuscular
junction.
For a discussion of genetic heterogeneity of CMS, see 608931.
CLINICAL FEATURES
Engel et al. (1977) reported a patient with a severely disabling CMS
associated with endplate acetylcholinesterase deficiency. Symptoms began
soon after birth with generalized weakness increased by exertion,
fatigability, hyporeflexia, and no response to AChE inhibitors. EMG
showed a decremental response to stimulation and a repetitive response
to single nerve stimulation. Miniature endplate potentials (MEPP) had
prolonged duration and decreased frequency. Electron microscopy of
muscle biopsy showed decreased nerve terminal size, reduced postsynaptic
membrane density, and focal degeneration of the postsynaptic folds.
Degenerating nuclei were also present. Histochemical analysis did not
detect AChE at the endplate. Engel et al. (1977) suggested a congenital
defect in the molecular assembly of AChE or its attachment to the
postsynaptic membrane.
Hutchinson et al. (1993) reported studies of the patient reported by
Engel et al. (1977) and 4 other patients, 2 of whom were sisters. All
patients had generalized weakness that was exacerbated by exertion, and
mild slowing of the pupillary light reflex; however, ophthalmoparesis
was not a constant feature. Electrophysiologic studies revealed a
decremental response to stimulation, prolonged endplate currents, and
reduced quantal release. All patients had absence of AChE from the
neuromuscular junction, which explained the lack of clinical benefit
from AChE inhibitors. Electron microscopy showed small nerve terminals,
abnormal encasement of the presynaptic membrane by Schwann cells, and
degeneration of the junctional folds and organelles in the junctional
sarcoplasm. Muscle extracts from 3 patients showed absence of the
collagen tail of AChE, while kinetic properties of the enzyme were
normal. Studies of the AChE catalytic subunit gene (ACHE; 100740)
revealed no abnormality in the exons that encode the domain to which the
tail subunit binds. Hutchinson et al. (1993) concluded that the
molecular defect resided in a faulty tail subunit, preventing assembly
of the AChE enzyme.
Jennekens et al. (1992) reported a 6-year-old boy with partial
deficiency of both endplate acetylcholinesterase and the
acetylcholinesterase receptor (see 608931).
In a study of 5 patients with congenital myasthenia associated with
endplate acetylcholinesterase deficiency, Camp et al. (1995) found that
the ACHE gene had a normal sequence and normal assembly of catalytic
subunits. The authors suggested that the defect resided in an altered
structure of the collagen-containing tail subunit or, alternatively, in
an alteration in a protein involved in promoting the assembly between
the catalytic subunit and tail unit.
Donger et al. (1998) reported a large consanguineous Spanish family in
which 6 of 11 sibs had CMS with endplate AChE deficiency. Age at onset
ranged from 6 to 10 years. By the second decade, all patients complained
of great fatigability on exertion. One of them presented with permanent
neck and upper limb weakness; another had generalized weakness.
Electrophysiologic studies performed on 4 patients showed impaired
muscle-nerve conduction, with decremental responses at 3 Hz, repetitive
responses to single motor nerve stimulation, and abnormal jitter. A
discrete ptosis, in the one who had generalized weakness, was indicative
of a mild myopathic syndrome. No anti-AChR antibody was detected.
Parenteral administration of anticholinesterase drugs had either no
benefit or worsening effect.
MOLECULAR GENETICS
In 6 patients with AChE deficiency, Ohno et al. (1998) identified 6
recessive mutations in the COLQ gene (603033.0001-603033.0006). Two of
the patients had previously been reported by Engel et al. (1977) and
Hutchinson et al. (1993).
In affected members of a consanguineous Spanish family with EAD, Donger
et al. (1998) identified a homozygous mutation in the COLQ gene
(603033.0007).
Shapira et al. (2002) reported 3 novel mutations in the COLQ gene in 8
patients with variable features of EAD: 1 patient was a compound
heterozygote; the other 7 patients, 6 Palestinian Arabs and 1 Iraqi Jew,
were all homozygous for a gly240-to-ter mutation (G240X; 603033.0010),
suggesting a founder effect. The patients with the G240X mutation
demonstrated phenotypic variability, including differences in age of
onset, disease progression, respiratory and feeding difficulties,
severity of weakness, and ophthalmoplegia.
*FIELD* SA
Greer and Schotland (1960)
*FIELD* RF
1. Camp, S.; Bon, S.; Li, Y.; Getman, D. K.; Engel, A. G.; Massoulie,
J.; Taylor, P.: Patients with congenital myasthenia associated with
end-plate acetylcholinesterase deficiency show normal sequence, mRNA
splicing, and assembly of catalytic subunits. J. Clin. Invest. 95:
333-340, 1995.
2. Donger, C.; Krejci, E.; Serradell, A. P.; Eymard, B.; Bon, S.;
Nicole, S.; Chateau, D.; Gary, F.; Fardeau, M.; Massoulie, J.; Guicheney,
P.: Mutation in the human acetylcholinesterase-associated collagen
gene, COLQ, is responsible for congenital myasthenic syndrome with
end-plate acetylcholinesterase deficiency (type Ic). Am. J. Hum.
Genet. 63: 967-975, 1998.
3. Engel, A. G.; Lambert, E. H.; Gomez, M. R.: A new myasthenic syndrome
with end-plate acetylcholinesterase deficiency, small nerve terminals,
and reduced acetylcholine release. Ann. Neurol. 1: 315-330, 1977.
4. Greer, M.; Schotland, M.: Myasthenia gravis in the newborn. Pediatrics 26:
101-108, 1960.
5. Hutchinson, D. O.; Walls, T. J.; Nakano, S.; Camp, S.; Taylor,
P.; Harper, C. M.; Groover, R. V.; Peterson, H. A.; Jamieson, D. G.;
Engel, A. G.: Congenital endplate acetylcholinesterase deficiency. Brain 116:
633-653, 1993.
6. Jennekens, F. G. I.; Hesselmans, L. F. G. M.; Veldman, H.; Jansen,
E. N. H.; Spaans, F.; Molenaar, P. C.: Deficiency of acetylcholine
receptors in a case of endplate acetylcholinesterase deficiency: a
histochemical investigation. Muscle Nerve 15: 63-72, 1992.
7. Ohno, K.; Brengman, J.; Tsujino, A.; Engel, A. G.: Human endplate
acetylcholinesterase deficiency caused by mutations in the collagen-like
tail subunit (ColQ) of the asymmetric enzyme. Proc. Nat. Acad. Sci. 95:
9654-9659, 1998.
8. Shapira, Y. A.; Sadeh, M. E.; Bergtraum, M. P.; Tsujino, A.; Ohno,
K.; Shen, X.-M.; Brengman, J.; Edwardson, S.; Matoth, I.; Engel, A.
G.: Three novel COLQ mutations and variation of phenotypic expressivity
due to G240X. Neurology 58: 603-609, 2002.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Ptosis;
Ophthalmoparesis;
Slow, delayed pupillary light reflex
RESPIRATORY:
Respiratory insufficiency due to muscle weakness
ABDOMEN:
[Gastrointestinal];
Poor feeding due to muscle weakness;
Dysphagia
SKELETAL:
[Spine];
Scoliosis;
Lordosis
MUSCLE, SOFT TISSUE:
Underdeveloped muscles;
Muscle biopsy shows type 2 fiber atrophy;
Muscle biopsy shows endplate myopathy (see details under NEUROLOGIC
heading)
NEUROLOGIC:
[Peripheral nervous system];
Generalized weakness due to defect at the neuromuscular junction;
Weakness is exacerbated by exertion;
Hypotonia;
Easy fatigability;
Limb weakness;
Dysarthria;
EMG shows decremental compound muscle action potential (CMAP) response
to repetitive nerve stimulation;
Multiple CMAP response to single nerve stimulation;
Prolonged miniature endplate potentials (MEPP);
Prolonged miniature endplate currents (MEPC);
Decreased frequency of MEPP;
Muscle biopsy shows absence of acetylcholinesterase (AChE) from neuromuscular
junction;
Muscle biopsy shows decreased size of nerve terminals;
Muscle biopsy shows decreased size of endplates;
Muscle biopsy shows decreased postsynaptic membrane density;
Muscle biopsy shows focal degeneration of postsynaptic junctional
folds;
Muscle biopsy shows abnormal encasement of presynaptic membrane by
Schwann cells
VOICE:
Weak cry
IMMUNOLOGY:
Absence of acetylcholine receptor (AChR) autoantibodies
MISCELLANEOUS:
Onset usually in infancy;
Later childhood onset has been reported;
Phenotypic variation in severity and symptoms;
No response or worsening with acetylcholinesterase inhibitors;
Symptoms progress with worsening myopathy
MOLECULAR BASIS:
Caused by mutation in the collagenic tail of endplate acetylcholinesterase
gene (COLQ, 603033.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/24/2004
*FIELD* ED
joanna: 10/11/2004
ckniffin: 9/29/2004
*FIELD* CN
Cassandra L. Kniffin - reorganized: 10/7/2004
Cassandra L. Kniffin - updated: 9/29/2004
Cassandra L. Kniffin - updated: 12/18/2002
Victor A. McKusick - updated: 10/22/1998
*FIELD* CD
Victor A. McKusick: 9/14/1998
*FIELD* ED
joanna: 10/13/2004
carol: 10/7/2004
ckniffin: 9/30/2004
ckniffin: 9/29/2004
carol: 1/3/2003
tkritzer: 12/23/2002
ckniffin: 12/18/2002
alopez: 4/15/2002
carol: 10/26/1998
terry: 10/22/1998
dkim: 9/21/1998
carol: 9/14/1998