RBCC Red Blood Cell Collection

VPS13A (CHAC, KIAA0986) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Vacuolar protein sorting-associated protein 13A (Chorea-acanthocytosis protein; Chorein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

Comments
Isoform Q96RL7-2 was detected.

UniProt Q96RL7
ID VP13A_HUMAN Reviewed; 3174 AA.
AC Q96RL7; Q5JSX9; Q5JSY0; Q5VYR5; Q702P4; Q709D0; Q86YF8; Q96S61;
read moreAC Q9H995; Q9Y2J1;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=Vacuolar protein sorting-associated protein 13A;
DE AltName: Full=Chorea-acanthocytosis protein;
DE AltName: Full=Chorein;
GN Name=VPS13A; Synonyms=CHAC, KIAA0986;
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], ALTERNATIVE SPLICING, AND VARIANTS CHAC
RP LYS-90; PRO-1452 AND CYS-2721.
RX PubMed=11381253; DOI=10.1038/88821;
RA Rampoldi L., Dobson-Stone C., Rubio J., Danek A., Chalmers R.,
RA Wood N.W., Verellen C., Ferrer X., Malandrini A., Fabrizi G.M.,
RA Brown R., Vance J., Pericak-Vance M., Rudolf G., Carre S., Alonso E.,
RA Manfredi M., Nemeth A.H., Monaco A.P.;
RT "A conserved sorting-associated protein is mutant in chorea-
RT acanthocytosis.";
RL Nat. Genet. 28:119-120(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11381254; DOI=10.1038/88825;
RA Ueno S., Maruki Y., Nakamura M., Tomemori Y., Kamae K., Tanabe H.,
RA Yamashita Y., Matsuda S., Kaneko S., Sano A.;
RT "The gene encoding a newly discovered protein, chorein, is mutated in
RT chorea-acanthocytosis.";
RL Nat. Genet. 28:121-122(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Lymphoblast;
RX PubMed=15498460; DOI=10.1016/j.ygeno.2004.04.012;
RA Velayos-Baeza A., Vettori A., Copley R.R., Dobson-Stone C.,
RA Monaco A.P.;
RT "Analysis of the human VPS13 gene family.";
RL Genomics 84:536-549(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1638-3174 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1749-2127, AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1850-3174 (ISOFORM 2).
RC TISSUE=Placenta, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2200-3174.
RC TISSUE=Teratocarcinoma;
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [9]
RP VARIANTS CHAC PRO-1095 AND ARG-2460, AND VARIANTS LEU-565; ALA-898;
RP LYS-1490; CYS-1587; ILE-1973; THR-2486 AND LEU-3172.
RX PubMed=12404112; DOI=10.1038/sj.ejhg.5200866;
RA Dobson-Stone C., Danek A., Rampoldi L., Hardie R.J., Chalmers R.M.,
RA Wood N.W., Bohlega S., Dotti M.T., Federico A., Shizuka M., Tanaka M.,
RA Watanabe M., Ikeda Y., Brin M., Goldfarb L.G., Karp B.I., Mohiddin S.,
RA Fananapazir L., Storch A., Fryer A.E., Maddison P., Sibon I.,
RA Trevisol-Bittencourt P.C., Singer C., Caballero I.R., Aasly J.O.,
RA Schmierer K., Dengler R., Hiersemenzel L.-P., Zeviani M., Meiner V.,
RA Lossos A., Johnson S., Mercado F.C., Sorrentino G., Dupre N.,
RA Rouleau G.A., Volkmann J., Arpa J., Lees A., Geraud G., Chouinard S.,
RA Nemeth A., Monaco A.P.;
RT "Mutational spectrum of the CHAC gene in patients with chorea-
RT acanthocytosis.";
RL Eur. J. Hum. Genet. 10:773-781(2002).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-161.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May play a role in the control of protein cycling
CC through the trans-Golgi network to early and late endosomes,
CC lysosomes and plasma membrane.
CC -!- INTERACTION:
CC P16333:NCK1; NbExp=3; IntAct=EBI-1752583, EBI-389883;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=A;
CC IsoId=Q96RL7-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q96RL7-2; Sequence=VSP_006550;
CC Name=3; Synonyms=Chorein 2A;
CC IsoId=Q96RL7-3; Sequence=VSP_014904;
CC Name=4; Synonyms=Chorein 1D;
CC IsoId=Q96RL7-4; Sequence=VSP_014905, VSP_014906;
CC -!- TISSUE SPECIFICITY: Widely expressed. Higher expression is found
CC in brain, heart, skeletal muscle and kidney.
CC -!- DISEASE: Choreoacanthocytosis (CHAC) [MIM:200150]: An autosomal
CC recessive neurodegenerative disorder characterized by the gradual
CC onset of hyperkinetic movements and abnormal erythrocyte
CC morphology. Basal ganglia atrophy in the brain is a pathological
CC feature of the disease. Other clinical symptoms include
CC psychiatric features, epilepsy, peripheral neuropathy, myopathy
CC and oral self-mutilation. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the VPS13 family.
CC -!- SIMILARITY: Contains 10 TPR repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20576.1; Type=Miscellaneous discrepancy; Note=Intron retention;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/VPS13A";
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DR EMBL; AF337532; AAK61861.1; -; mRNA.
DR EMBL; AB054005; BAB59128.1; -; mRNA.
DR EMBL; AJ608769; CAE75581.1; -; mRNA.
DR EMBL; AJ626859; CAF25186.1; -; mRNA.
DR EMBL; AL158159; CAI40935.1; -; Genomic_DNA.
DR EMBL; AL353710; CAI40935.1; JOINED; Genomic_DNA.
DR EMBL; AL359204; CAI40935.1; JOINED; Genomic_DNA.
DR EMBL; AL158159; CAI40936.1; -; Genomic_DNA.
DR EMBL; AL353710; CAI40936.1; JOINED; Genomic_DNA.
DR EMBL; AL359204; CAI40936.1; JOINED; Genomic_DNA.
DR EMBL; AL353710; CAH74105.1; -; Genomic_DNA.
DR EMBL; AL158159; CAH74105.1; JOINED; Genomic_DNA.
DR EMBL; AL359204; CAH74105.1; JOINED; Genomic_DNA.
DR EMBL; AL353710; CAH74106.1; -; Genomic_DNA.
DR EMBL; AL158159; CAH74106.1; JOINED; Genomic_DNA.
DR EMBL; AL359204; CAH74106.1; JOINED; Genomic_DNA.
DR EMBL; AL359204; CAI39537.1; -; Genomic_DNA.
DR EMBL; AL158159; CAI39537.1; JOINED; Genomic_DNA.
DR EMBL; AL353710; CAI39537.1; JOINED; Genomic_DNA.
DR EMBL; AL359204; CAI39538.1; -; Genomic_DNA.
DR EMBL; AL158159; CAI39538.1; JOINED; Genomic_DNA.
DR EMBL; AL353710; CAI39538.1; JOINED; Genomic_DNA.
DR EMBL; AB023203; BAA76830.1; -; mRNA.
DR EMBL; BC020576; AAH20576.1; ALT_SEQ; mRNA.
DR EMBL; BC041852; AAH41852.1; -; mRNA.
DR EMBL; AK022967; BAB14337.1; -; mRNA.
DR RefSeq; NP_001018047.1; NM_001018037.1.
DR RefSeq; NP_001018048.1; NM_001018038.2.
DR RefSeq; NP_056001.1; NM_015186.3.
DR RefSeq; NP_150648.2; NM_033305.2.
DR UniGene; Hs.459790; -.
DR UniGene; Hs.662256; -.
DR ProteinModelPortal; Q96RL7; -.
DR IntAct; Q96RL7; 7.
DR PhosphoSite; Q96RL7; -.
DR DMDM; 71152975; -.
DR PaxDb; Q96RL7; -.
DR PRIDE; Q96RL7; -.
DR Ensembl; ENST00000357409; ENSP00000349985; ENSG00000197969.
DR Ensembl; ENST00000360280; ENSP00000353422; ENSG00000197969.
DR Ensembl; ENST00000376634; ENSP00000365821; ENSG00000197969.
DR Ensembl; ENST00000376636; ENSP00000365823; ENSG00000197969.
DR GeneID; 23230; -.
DR KEGG; hsa:23230; -.
DR UCSC; uc004akr.3; human.
DR CTD; 23230; -.
DR GeneCards; GC09P079793; -.
DR HGNC; HGNC:1908; VPS13A.
DR HPA; HPA021652; -.
DR HPA; HPA021662; -.
DR MIM; 200150; phenotype.
DR MIM; 605978; gene.
DR neXtProt; NX_Q96RL7; -.
DR Orphanet; 2388; Choreoacanthocytosis.
DR PharmGKB; PA26444; -.
DR eggNOG; COG5043; -.
DR HOVERGEN; HBG079736; -.
DR OMA; YAIHGIL; -.
DR OrthoDB; EOG7S4X52; -.
DR GeneWiki; VPS13A; -.
DR GenomeRNAi; 23230; -.
DR NextBio; 44845; -.
DR PRO; PR:Q96RL7; -.
DR ArrayExpress; Q96RL7; -.
DR Bgee; Q96RL7; -.
DR Genevestigator; Q96RL7; -.
DR GO; GO:0031045; C:dense core granule; IEA:Ensembl.
DR GO; GO:0005622; C:intracellular; NAS:UniProtKB.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0006895; P:Golgi to endosome transport; NAS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0008104; P:protein localization; NAS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR InterPro; IPR015412; Autophagy-rel_C.
DR InterPro; IPR026847; VPS13.
DR InterPro; IPR026854; VPS13A_N.
DR InterPro; IPR009543; VPSAP_dom.
DR PANTHER; PTHR16166; PTHR16166; 1.
DR Pfam; PF09333; ATG_C; 1.
DR Pfam; PF12624; Chorein_N; 1.
DR Pfam; PF06650; DUF1162; 1.
DR PROSITE; PS50005; TPR; FALSE_NEG.
DR PROSITE; PS50293; TPR_REGION; FALSE_NEG.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disease mutation; Epilepsy;
KW Neurodegeneration; Polymorphism; Protein transport;
KW Reference proteome; Repeat; TPR repeat; Transport.
FT CHAIN 1 3174 Vacuolar protein sorting-associated
FT protein 13A.
FT /FTId=PRO_0000106277.
FT REPEAT 212 245 TPR 1.
FT REPEAT 373 406 TPR 2.
FT REPEAT 537 575 TPR 3.
FT REPEAT 1256 1289 TPR 4.
FT REPEAT 1291 1320 TPR 5.
FT REPEAT 2009 2041 TPR 6.
FT REPEAT 2568 2601 TPR 7.
FT REPEAT 2717 2751 TPR 8.
FT REPEAT 2860 2898 TPR 9.
FT REPEAT 3086 3119 TPR 10.
FT VAR_SEQ 1040 1078 Missing (in isoform 3).
FT /FTId=VSP_014904.
FT VAR_SEQ 3064 3174 VMENGRFAKYKYFTHVMINKTDMLMITRRGVLFVTKGTFGQ
FT LTCEWQYSFDEFTKEPFIVHGRRLRIEAKERVKSVFHAREF
FT GKIINFKTPEDARWILTKLQEAREPSPSL -> KIQFYREW
FT IMTHSSSSDDDDDDDDDDESDLNH (in isoform 2).
FT /FTId=VSP_006550.
FT VAR_SEQ 3064 3069 VMENGR -> ASKSLI (in isoform 4).
FT /FTId=VSP_014905.
FT VAR_SEQ 3070 3174 Missing (in isoform 4).
FT /FTId=VSP_014906.
FT VARIANT 90 90 I -> K (in CHAC; dbSNP:rs28939379).
FT /FTId=VAR_038420.
FT VARIANT 161 161 R -> H (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036324.
FT VARIANT 565 565 F -> L.
FT /FTId=VAR_058114.
FT VARIANT 898 898 V -> A (in dbSNP:rs78048112).
FT /FTId=VAR_058115.
FT VARIANT 1095 1095 A -> P (in CHAC).
FT /FTId=VAR_058116.
FT VARIANT 1452 1452 S -> P (in CHAC).
FT /FTId=VAR_012803.
FT VARIANT 1490 1490 R -> K (in dbSNP:rs76077278).
FT /FTId=VAR_058117.
FT VARIANT 1587 1587 Y -> C (in dbSNP:rs149840356).
FT /FTId=VAR_058118.
FT VARIANT 1973 1973 V -> I (in dbSNP:rs41289969).
FT /FTId=VAR_058119.
FT VARIANT 2460 2460 W -> R (in CHAC).
FT /FTId=VAR_058120.
FT VARIANT 2486 2486 I -> T (in dbSNP:rs141138349).
FT /FTId=VAR_058121.
FT VARIANT 2721 2721 Y -> C (in CHAC).
FT /FTId=VAR_038421.
FT VARIANT 3172 3172 P -> L.
FT /FTId=VAR_058122.
FT CONFLICT 1198 1198 K -> R (in Ref. 1; AAK61861).
FT CONFLICT 1850 1850 L -> R (in Ref. 6; AAH41852).
FT CONFLICT 1880 1880 I -> F (in Ref. 6; AAH41852).
FT CONFLICT 2281 2281 G -> E (in Ref. 7; BAB14337).
FT CONFLICT 2354 2354 K -> R (in Ref. 6; AAH41852).
FT CONFLICT 2413 2413 T -> R (in Ref. 7; BAB14337).
FT CONFLICT 2567 2567 K -> E (in Ref. 7; BAB14337).
SQ SEQUENCE 3174 AA; 360276 MW; 58C8EC818E3350F4 CRC64;
MVFESVVVDV LNRFLGDYVV DLDTSQLSLG IWKGAVALKN LQIKENALSQ LDVPFKVKVG
HIGNLKLIIP WKNLYTQPVE AVLEEIYLLI VPSSRIKYDP LKEEKQLMEA KQQELKRIEE
AKQKVVDQEQ HLPEKQDTFA EKLVTQIIKN LQVKISSIHI RYEDDITNRD KPLSFGISLQ
NLSMQTTDQY WVPCLHDETE KLVRKLIRLD NLFAYWNVKS QMFYLSDYDN SLDDLKNGIV
NENIVPEGYD FVFRPISANA KLVMNRRSDF DFSAPKINLE IELHNIAIEF NKPQYFSIME
LLESVDMMAQ NLPYRKFKPD VPLHHHAREW WAYAIHGVLE VNVCPRLWMW SWKHIRKHRQ
KVKQYKELYK KKLTSKKPPG ELLVSLEELE KTLDVFNITI ARQTAEVEVK KAGYKIYKEG
VKDPEDNKGW FSWLWSWSEQ NTNEQQPDVQ PETLEEMLTP EEKALLYEAI GYSETAVDPT
LLKTFEALKF FVHLKSMSIV LRENHQKPEL VDIVIEEFST LIVQRPGAQA IKFETKIDSF
HITGLPDNSE KPRLLSSLDD AMSLFQITFE INPLDETVSQ RCIIEAEPLE IIYDARTVNS
IVEFFRPPKE VHLAQLTAAT LTKLEEFRSK TATGLLYIIE TQKVLDLKIN LKASYIIVPQ
DGIFSPTSNL LLLDLGHLKV TSKSRSELPD VKQGEANLKE IMDRAYDSFD IQLTSVQLLY
SRVGDNWREA RKLSVSTQHI LVPMHFNLEL SKAMVFMDVR MPKFKIYGKL PLISLRISDK
KLQGIMELIE SIPKPEPVTE VSAPVKSFQI QTSTSLGTSQ ISQKIIPLLE LPSVSEDDSE
EEFFDAPCSP LEEPLQFPTG VKSIRTRKLQ KQDCSVNMTT FKIRFEVPKV LIEFYHLVGD
CELSVVEILV LGLGAEIEIR TYDLKANAFL KEFCLKCPEY LDENKKPVYL VTTLDNTMED
LLTLEYVKAE KNVPDLKSTY NNVLQLIKVN FSSLDIHLHT EALLNTINYL HNILPQSEEK
SAPVSTTETE DKGDVIKKLA LKLSTNEDII TLQILAELSC LQIFIQDQKC NISEIKIEGL
DSEMIMRPSE TEINAKLRNI IVLDSDITAI YKKAVYITGK EVFSFKMVSY MDATAGSAYT
DMNVVDIQVN LIVGCIEVVF VTKFLYSILA FIDNFQAAKQ ALAEATVQAA GMAATGVKEL
AQRSSRMALD INIKAPVVVI PQSPVSENVF VADFGLITMT NTFHMITESQ SSPPPVIDLI
TIKLSEMRLY RSRFINDAYQ EVLDLLLPLN LEVVVERNLC WEWYQEVPCF NVNAQLKPME
FILSQEDITT IFKTLHGNIW YEKDGSASPA VTKDQYSATS GVTTNASHHS GGATVVTAAV
VEVHSRALLV KTTLNISFKT DDLTMVLYSP GPKQASFTDV RDPSLKLAEF KLENIISTLK
MYTDGSTFSS FSLKNCILDD KRPHVKKATP RMIGLTVGFD KKDMMDIKYR KVRDGCVTDA
VFQEMYICAS VEFLQTVANV FLEAYTTGTA VETSVQTWTA KEEVPTQESV KWEINVIIKN
PEIVFVADMT KNDAPALVIT TQCEICYKGN LENSTMTAAI KDLQVRACPF LPVKRKGKIT
TVLQPCDLFY QTTQKGTDPQ VIDMSVKSLT LKVSPVIINT MITITSALYT TKETIPEETA
SSTAHLWEKK DTKTLKMWFL EESNETEKIA PTTELVPKGE MIKMNIDSIF IVLEAGIGHR
TVPMLLAKSR FSGEGKNWSS LINLHCQLEL EVHYYNEMFG VWEPLLEPLE IDQTEDFRPW
NLGIKMKKKA KMAIVESDPE EENYKVPEYK TVISFHSKDQ LNITLSKCGL VMLNNLVKAF
TEAATGSSAD FVKDLAPFMI LNSLGLTISV SPSDSFSVLN IPMAKSYVLK NGESLSMDYI
RTKDNDHFNA MTSLSSKLFF ILLTPVNHST ADKIPLTKVG RRLYTVRHRE SGVERSIVCQ
IDTVEGSKKV TIRSPVQIRN HFSVPLSVYE GDTLLGTASP ENEFNIPLGS YRSFIFLKPE
DENYQMCEGI DFEEIIKNDG ALLKKKCRSK NPSKESFLIN IVPEKDNLTS LSVYSEDGWD
LPYIMHLWPP ILLRNLLPYK IAYYIEGIEN SVFTLSEGHS AQICTAQLGK ARLHLKLLDY
LNHDWKSEYH IKPNQQDISF VSFTCVTEME KTDLDIAVHM TYNTGQTVVA FHSPYWMVNK
TGRMLQYKAD GIHRKHPPNY KKPVLFSFQP NHFFNNNKVQ LMVTDSELSN QFSIDTVGSH
GAVKCKGLKM DYQVGVTIDL SSFNITRIVT FTPFYMIKNK SKYHISVAEE GNDKWLSLDL
EQCIPFWPEY ASSKLLIQVE RSEDPPKRIY FNKQENCILL RLDNELGGII AEVNLAEHST
VITFLDYHDG AATFLLINHT KNELVQYNQS SLSEIEDSLP PGKAVFYTWA DPVGSRRLKW
RCRKSHGEVT QKDDMMMPID LGEKTIYLVS FFEGLQRIIL FTEDPRVFKV TYESEKAELA
EQEIAVALQD VGISLVNNYT KQEVAYIGIT SSDVVWETKP KKKARWKPMS VKHTEKLERE
FKEYTESSPS EDKVIQLDTN VPVRLTPTGH NMKILQPHVI ALRRNYLPAL KVEYNTSAHQ
SSFRIQIYRI QIQNQIHGAV FPFVFYPVKP PKSVTMDSAP KPFTDVSIVM RSAGHSQISR
IKYFKVLIQE MDLRLDLGFI YALTDLMTEA EVTENTEVEL FHKDIEAFKE EYKTASLVDQ
SQVSLYEYFH ISPIKLHLSV SLSSGREEAK DSKQNGGLIP VHSLNLLLKS IGATLTDVQD
VVFKLAFFEL NYQFHTTSDL QSEVIRHYSK QAIKQMYVLI LGLDVLGNPF GLIREFSEGV
EAFFYEPYQG AIQGPEEFVE GMALGLKALV GGAVGGLAGA ASKITGAMAK GVAAMTMDED
YQQKRREAMN KQPAGFREGI TRGGKGLVSG FVSGITGIVT KPIKGAQKGG AAGFFKGVGK
GLVGAVARPT GGIIDMASST FQGIKRATET SEVESLRPPR FFNEDGVIRP YRLRDGTGNQ
MLQVMENGRF AKYKYFTHVM INKTDMLMIT RRGVLFVTKG TFGQLTCEWQ YSFDEFTKEP
FIVHGRRLRI EAKERVKSVF HAREFGKIIN FKTPEDARWI LTKLQEAREP SPSL
//

MIM 200150
*RECORD*
*FIELD* NO
200150
*FIELD* TI
#200150 CHOREOACANTHOCYTOSIS; CHAC
;;LEVINE-CRITCHLEY SYNDROME;;
ACANTHOCYTOSIS WITH NEUROLOGIC DISORDER;;
read moreNEUROACANTHOCYTOSIS;;
CHOREA-ACANTHOCYTOSIS
*FIELD* TX
A number sign (#) is used with this entry because choreoacanthocytosis
can be caused by homozygous or compound heterozygous mutation in the
VPS13A gene (605978), which encodes chorein, on chromosome 9q21.

DESCRIPTION

Choreoacanthocytosis (CHAC) is a rare disorder characterized by
progressive neurodegeneration and red cell acanthocytosis, with onset in
the third to fifth decade of life (Rubio et al., 1997).

See also McLeod syndrome (300842) for a phenotypically similar disorder.

CLINICAL FEATURES

Critchley et al. (1967, 1968) described an adult form of acanthocytosis
associated with neurologic abnormalities and apparently normal serum
lipoproteins. The proband had onset in his mid-twenties of generalized
weakness and involuntary movements, including grimacing, dystonia, and
chorea. Orofacial movements were especially dramatic, and the patient
had multiple bite lesions on his lips, tongue, and cheeks. The
neurologic manifestations resembled those of the Gilles de la Tourette
syndrome (137580) or Huntington disease (143100). Four of the proband's
sibs had neurologic manifestations. A niece had acanthocytes and a
neurologic disorder suggesting Friedreich ataxia (229300).

Estes et al. (1967) and Levine et al. (1968) reported a family in which
19 persons in 4 generations had some degree of neurologic abnormalities,
15 with, and 4 without, acanthocytosis. Acanthocytes averaged from 1 to
20% of the total erythrocyte count, and there was no obvious association
between the degree of acanthocytosis and the severity of the neurologic
disability. There were no demonstrable quantitative defects of low
density (beta) or high density (alpha) lipoproteins. Major neurologic
symptoms included muscle weakness and atrophy, leg cramps, disturbances
of coordination, hyporeflexia, chorea, and seizures. Inheritance was
consistent with autosomal dominance. Levine et al. (1968) concluded that
the disorder was neuronal.

Critchley et al. (1970) reported a single case from England, a woman who
showed self-mutilation of the tongue, lips, and cheeks. Another family
was reported by Aminoff (1972). Wasting of girdle and proximal limb
muscles, absent tendon reflexes, and disturbance of bladder function
were other features.

Cederbaum et al. (1971) and Bird et al. (1978) observed a consanguineous
family in which 3 adult sibs developed progressive chorea and dementia
similar to Huntington disease (143100), but with acanthocytes in the
peripheral blood. No malabsorption or abnormalities of serum
beta-lipoprotein were found. The proband was a 41-year-old male, and an
affected brother and sister had died at ages 32 and 39 years. Postmortem
examination showed marked neuronal loss and gliosis of the caudate and
putamen. Two children of the proband were healthy. The authors suggested
that the same disorder may have been present in the family of Critchley
et al. (1967), although the pattern of inheritance in that family
appeared to be autosomal dominant. In a patient with acanthocytosis and
degeneration of the basal ganglia, Copeland et al. (1982) found an
abnormally high level of a protein in the 100,000 MW range on 2-D
O'Farrell gel electrophoresis of red cell membranes. This patient was
from the family reported by Bird et al. (1978) (Motulsky, 1982).

Yamamoto et al. (1982) reported 2 sibs with neuroacanthocytosis with
normal serum lipoprotein levels. Features included orolingual tic-like
movements associated with vocalization, biting of the lip and tongue,
dysphagia, subtle parkinsonism, and chorea.

Gross et al. (1985) reported a 46-year-old man of Hispanic Puerto Rican
ancestry who had familial amyotrophic chorea with acanthocytosis
(FACWA). At age 36 years, he developed progressive orofacial dyskinesia,
dysarthria, dysphagia, and chorea of the trunk and limbs. Generalized
tonic-clonic seizures appeared at age 40. Examination at age 46 showed
the abnormal movements, as well as atrophy and weakness of the limb
muscles and areflexia. Laboratory studies showed acanthocytosis on
peripheral blood smear and increased serum creatine kinase. Family
history revealed a brother who was less severely affected. The index
patient also had increased free sialic acid, which the authors
attributed to tissue destruction; the brother did not have this finding.
Gross et al. (1985) noted the phenotypic similarity to the family
reported by Estes et al. (1967).

Hardie et al. (1991) reviewed neuroacanthocytosis on the basis of 19
cases, 12 familial and 7 nonfamilial. The mean age at onset was 32 years
(range, 8-62) and the clinical course was usually progressive with
cognitive impairment, psychiatric features, and organic personality
changes in over half the cases. More than one-third of the cases had
seizures. Orofaciolingual involuntary movements and pseudobulbar
disturbance commonly caused dysphagia and dysarthria. Chorea was seen in
almost all cases, and dystonia, tics, and akinetic-rigid features also
occurred. CT imaging showed cerebral atrophy, but caudate atrophy was
seen less commonly. Postmortem examination in 1 case revealed extensive
neuronal loss and gliosis affecting the striatum, pallidum, and
substantia nigra. Kartsounis and Hardie (1996) reviewed the clinical
features of 19 reported cases of neuroacanthocytosis and found that the
most consistent neurologic findings were impairment of frontal lobe
function and psychiatric morbidity, in a pattern suggesting subcortical
dementia.

See Kay (1991) for a discussion of band 3 protein (109270) abnormalities
in autosomal recessive choreoacanthocytosis.

In 3 patients with neuroacanthocytosis, Rinne et al. (1994) demonstrated
reduced neuronal density in the substantia nigra. As in Parkinson
disease, the ventral lateral region was most severely affected, but with
a slightly more diffuse distribution.

Sorrentino et al. (1999) described late appearance of acanthocytes in
the course of chorea-acanthocytosis. The patient was a 37-year-old man
whose parents were second cousins. Onset was reported to be at the age
of 20 years with personality changes, sexual disinhibition,
aggressiveness, and sporadic orofaciolingual dyskinesias. Persistent
choreic movements of the head, shoulders, trunk, and limbs appeared
later. At 28 years, he developed sporadic, generalized tonic-clonic
seizures which disappeared after the age of 33 years. At that time,
neurologic examination showed self mutilation of tongue and lip,
dysarthria, mild diffuse muscle atrophy, and lack of deep tendon
reflexes. Blood smears failed to show acanthocytes. Three years later
when he was restudied for progression of neurologic manifestations, a
fresh Wright stain revealed 51% acanthocytes.

Requena Caballero et al. (2000) described a 34-year-old male, son of
consanguineous parents, who had a progressive neurologic illness
characterized by seizures, tics, choreic movements, and mood changes.
Acanthocytosis was present in the blood, and serum beta-lipoprotein was
normal. No KX (314850) changes of McLeod syndrome were found. Serial
neuroimaging studies demonstrated progressive caudate atrophy. Elevated
creatine kinase and muscle biopsy showed a nonspecific myopathy. Genetic
study demonstrated linkage of the disorder to the 9q21 region.

Lossos et al. (2005) reported 3 unrelated Jewish patients with
choreoacanthocytosis confirmed by genetic analysis (605978.0006;
605978.0007). One of the patients had trichotillomania beginning in
adolescence, 2 decades before diagnosis of CHAC. She also experienced
postpartum exacerbation of CHAC. Another patient showed increased serum
creatine kinase and hepatosplenomegaly approximately 10 years before
other symptoms of CHAC developed.

Gradstein et al. (2005) described the eye movement abnormalities in 3
patients with CHAC. All had degeneration of the basal ganglia on MRI
typical of CHAC. Their eye movement findings suggested brainstem
involvement as an additional site of neurodegeneration outside the basal
ganglia in CHAC. All 3 patients were later reported by Dobson-Stone et
al. (2002) to have mutations in the VSP13A gene.

Ruiz-Sandoval et al. (2007) reported 2 Mexican mestizo sisters, born of
consanguineous parents, with choreoacanthocytosis associated with a
homozygous VPS13A mutation (605978.0009). The proband had onset at age
32 years and showed severe progression of the disorder; at age 42, she
was emaciated, anarthric, and reactive only to simple commands. In
contrast, her sister had onset at age 45 years and primarily showed
motor and verbal tics, paranoid behavior, and depression. Ruiz-Sandoval
et al. (2007) noted the clinical heterogeneity of the disorder in this
family despite the patients having the same mutation.

INHERITANCE

Spitz et al. (1985) reported 2 brothers from a consanguineous family
with motor and vocal tics, parkinsonism, distal muscular atrophy, and
acanthocytosis. The neurologic features became most apparent in their
thirties. Villegas et al. (1987) reported 2 affected sibs whose parents
were normal. The patients did not have anemia or signs of hemolysis.

Vance et al. (1987) reported 4 affected patients from 3 families, and
concluded that the inheritance was most likely autosomal recessive. Two
of the 3 propositi were initially diagnosed as having Huntington
disease. MRI showed atrophy of the caudate and putamen. Obligate
heterozygotes did not show acanthocytosis. The authors noted that the
disorder may be more frequent in Japan than elsewhere (Kito et al.,
1980; Nagashima et al., 1979; Yamamoto et al., 1982). Vance et al.
(1987) reviewed the literature and concluded that of 9 families in which
there were 2 or more affected members, 2 were probably autosomal
dominant and 7 were autosomal recessive.

DIAGNOSIS

- Differential Diagnosis

Walker et al. (2002) reported a family in which 3 members were affected
with what the authors thought was autosomal dominant
choreoacanthocytosis. The 56-year-old proband had initially been
diagnosed with Huntington disease (143100). All 3 patients had 30 to 35%
acanthocytosis on peripheral blood smear. However, in affected members
of this family, Walker et al. (2003) identified trinucleotide repeat
expansions in the junctophilin-3 gene (605268.0001), confirming a
diagnosis of Huntington disease-like-2 (HDL2; 606438). Walker et al.
(2003) suggested that HDL2 should be considered in the differential
diagnosis of choreoacanthocytosis.

MAPPING

Rubio et al. (1997) performed linkage studies of 11 families segregating
for CHAC that were of diverse geographic origin. They found linkage in
all families to a 6-cM region of 9q21 that is flanked by the recombinant
markers GATA89a11 and D9S1843. A maximum 2-point lod score of 7.1 at
theta = 0.0 was achieved for D9S1867. The results of these studies were
confirmed by homozygosity-by-descent analysis in offspring from
consanguineous marriages. Together, these data provided strong evidence
for the involvement of a single locus for CHAC.

MOLECULAR GENETICS

In the 11 CHAC families reported by Rubio et al. (1997), Rampoldi et al.
(2001) identified 16 different mutations in the gene encoding chorein
(see, e.g., 605978.0001).

In 4 affected patients from 3 Japanese kindreds with CHAC, Ueno et al.
(2001) identified homozygosity for a deletion in the VPS13A gene
(605978.0003). The unaffected parents were heterozygous for the
deletion. Haplotype analysis indicated a founder effect.

Among 43 patients with choreoacanthocytosis, Dobson-Stone et al. (2002)
identified 57 different mutations distributed throughout the CHAC gene
(see, e.g., 605978.0004). In 7 patients, only 1 heterozygous mutation
was found; in 4 patients, no disease mutations were found. The authors
noted that small gene deletions or rearrangements may not have been
detected in these patients.

In 2 affected sibs from a Japanese family with choreoacanthocytosis with
apparent autosomal dominant inheritance, Saiki et al. (2003) identified
heterozygosity for mutation in the CHAC gene (605978.0005). In an
erratum, the authors stated that an error in sequencing had occurred and
the inheritance pattern should have been reported as autosomal recessive
(pseudodominant).

Dobson-Stone et al. (2005) identified a homozygous 37-kb deletion in the
VPS13A gene (605978.0008) in affected members of 3 French Canadian
families with choreoacanthocytosis. Haplotype analysis indicated a
founder effect.

NOMENCLATURE

Sakai et al. (1985) suggested the term 'Levine-Critchley syndrome' as
the best designation for this disorder. They considered the term
choreoacanthocytosis inappropriate because tics, dystonia, or
parkinsonism may dominate the clinical picture (Spitz et al., 1985).
'Neuroacanthocytosis' was also considered inappropriate because it might
include the Bassen-Kornzweig syndrome (200100). Jankovic et al. (1985)
noted that there are 2 other neuroacanthocytoses: one associated with
hypobetalipoproteinemia (615558) and another that is part of the McLeod
syndrome.

*FIELD* SA
Betts et al. (1970); Vance et al. (1994)
*FIELD* RF
1. Aminoff, M. J.: Acanthocytosis and neurological disease. Brain 95:
749-760, 1972.

2. Betts, J. J.; Nicholson, J. T.; Critchley, E. M. R.: Acanthocytosis
with normolipoproteinaemia: biophysical aspects. Postgrad. Med. J. 46:
702-707, 1970.

3. Bird, T. D.; Cederbaum, S. D.; Valpey, R. W.; Stahl, W. L.: Familial
degeneration of the basal ganglia with acanthocytosis: a clinical,
neuropathological and neurochemical study. Ann. Neurol. 3: 253-258,
1978.

4. Cederbaum, S. J.; Heywood, D.; Aigner, R.; Motulsky, A. G.: Progressive
chorea, dementia and acanthocytosis: a genocopy of Huntington's chorea.
(Abstract) Clin. Res. 19: 177 only, 1971.

5. Copeland, B. R.; Todd, S. A.; Furlong, C. E.: High resolution
two-dimensional gel electrophoresis of human erythrocyte membrane
proteins. Am. J. Hum. Genet. 34: 15-31, 1982.

6. Critchley, E. M. R.; Betts, J. J.; Nicholson, J. T.; Weatherall,
D. J.: Acanthocytosis, normolipoproteinaemia and multiple tics. Postgrad.
Med. J. 46: 698-701, 1970.

7. Critchley, E. M. R.; Clark, D. B.; Wikler, A.: An adult form of
acanthocytosis. Trans. Am. Neurol. Assoc. 92: 132-137, 1967.

8. Critchley, E. M. R.; Clark, D. B.; Wikler, A.: Acanthocytosis
and neurological disorder without betalipoproteinemia. Arch. Neurol. 18:
134-140, 1968.

9. Dobson-Stone, C.; Danek, A.; Rampoldi, L.; Hardie, R. J.; Chalmers,
R. M.; Wood, N. W.; Bohlega, S.; Dotti, M. T.; Federico, A.; Shizuka,
M.; Tanaka, M.; Watanabe, M.; and 32 others: Mutational spectrum
of the CHAC gene in patients with chorea-acanthocytosis. Europ. J.
Hum. Genet. 10: 773-781, 2002.

10. Dobson-Stone, C.; Velayos-Baeza, A.; Jansen, A.; Andermann, F.;
Dubeau, F.; Robert, F.; Summers, A.; Lang, A. E.; Chouinard, S.; Danek,
A.; Andermann, E.; Monaco, A. P.: Identification of a VPS13A founder
mutation in French Canadian families with chorea-acanthocytosis. Neurogenetics 6:
151-158, 2005.

11. Estes, J. W.; Morley, T. J.; Levine, I. M.; Emerson, C. P.: A
new hereditary acanthocytosis syndrome. Am. J. Med. 42: 868-881,
1967.

12. Gradstein, L.; Danek, A.; Grafman, J.; FitzGibbon, E. J.: Eye
movements in chorea-acanthocytosis. Invest. Ophthal. Vis. Sci. 46:
1979-1987, 2005.

13. Gross, K. B.; Skrivanek, J. A.; Carlson, K. C.; Kaufman, D. M.
: Familial amyotrophic chorea with acanthocytosis: new clinical and
laboratory investigations. Arch. Neurol. 42: 753-756, 1985.

14. Hardie, R. J.; Pullon, H. W. H.; Harding, A. E.; Owen, J. S.;
Pires, M.; Daniels, G. L.; Imai, Y.; Misra, V. P.; King, R. H. M.;
Jacobs, J. M.; Tippett, P.; Duchen, L. W.; Thomas, P. K.; Marsden,
C. D.: Neuroacanthocytosis: a clinical haematological and pathological
study of 19 cases. Brain 114: 13-49, 1991.

15. Jankovic, J.; Killian, J. M.; Spitz, M. C.: Neuroacanthocytosis
syndrome and choreoacanthocytosis (Levine-Critchley syndrome). (Letter) Neurology 35:
1679, 1985.

16. Kartsounis, L. D.; Hardie, R. J.: The pattern of cognitive impairments
in neuroacanthocytosis: a frontosubcortical dementia. Arch. Neurol. 53:
77-80, 1996.

17. Kay, M. M. B.: Band 3 in aging and neurological disease. Ann.
N.Y. Acad. Sci. 621: 179-204, 1991.

18. Kito, S.; Itoga, E.; Kiroshige, Y.; Matsamoto, N.; Miwa, S.:
A pedigree of amyotrophic chorea with acanthocytosis. Arch. Neurol. 37:
514-517, 1980.

19. Levine, I. M.; Estes, J. W.; Looney, J. M.: Hereditary neurological
disease with acanthocytosis: a new syndrome. Arch. Neurol. 19: 403-409,
1968.

20. Lossos, A.; Dobson-Stone, C.; Monaco, A. P.; Soffer, D.; Rahamim,
E.; Newman, J. P.; Mohiddin, S.; Fananapazir, L.; Lerer, I.; Linetsky,
E.; Reches, A.; Argov, Z.; Abramsky, O.; Gadoth, N.; Sadeh, M.; Gomori,
J. M.; Boher, M.; Meiner, V.: Early clinical heterogeneity in choreoacanthocytosis. Arch.
Neurol. 62: 611-614, 2005.

21. Motulsky, A. G.: Personal Communication. Seattle, Washington
4/21/1982.

22. Nagashima, T.; Iwashita, H.; Kuroiwa, Y.; Ohnishi, S.: Chorea-acanthocytosis:
a report of a family. Clin. Neurol. 19: 609-615, 1979.

23. Rampoldi, L.; Dobson-Stone, C.; Rubio, J. P.; Danek, A.; Chalmers,
R. M.; Wood, N. W.; Verellen, C.; Ferrer, X.; Malandrini, A.; Fabrizi,
G. M.; Brown, R.; Vance, J.; Pericak-Vance, M.; Rudolf, G.; Carre,
S.; Alonso, E.; Manfredi, M.; Nemeth, A. H.; Monaco, A. P.: A conserved
sorting-associated protein is mutant in chorea-acanthocytosis. Nature
Genet. 28: 119-120, 2001.

24. Requena Caballero, I.; Arias Gomez, M.; Lema Devesa, C.; Sanchez
Herrero, J.; Barros Angueira, F.; Coton Vilas, J. C.: Corea-acantocitosis
autosomica recesiva ligada a 9q21. Neurologia 15: 132-135, 2000.

25. Rinne, J. O.; Daniel, S. E.; Scaravilli, F.; Harding, A. E.; Marsden,
C. D.: Nigral degeneration in neuroacanthocytosis. Neurology 44:
1629-1632, 1994.

26. Rubio, J. P.; Danek, A.; Stone, C.; Chalmers, R.; Wood, N.; Verellen,
C.; Ferrer, X.; Malandrini, A.; Fabrizi, G. M.; Manfredi, M.; Vance,
J.; Pericak-Vance, M.; Brown, R.; Rudolf, G.; Picard, F.; Alonso,
E.; Brin, M.; Nemeth, A. H.; Farrall, M.; Monaco, A. P.: Chorea-acanthocytosis:
genetic linkage to chromosome 9q21. Am. J. Hum. Genet. 61: 899-908,
1997.

27. Ruiz-Sandoval, J. L.; Garcia-Navarro, V.; Chiquete, E.; Dobson-Stone,
C.; Monaco, A. P.; Alvarez-Palazuelos, L. E.; Padilla-Martinez, J.
J.; Barrera-Chairez, E.; Rodriguez-Figueroa, E. I.; Perez-Garcia,
G.: Choreoacanthocytosis in a Mexican family. Arch. Neurol. 64:
1661-1664, 2007.

28. Saiki, S.; Sakai, K.; Kitagawa, Y.; Saiki, M.; Kataoka, S.; Hirose,
G.: Mutation in the CHAC gene in a family of autosomal dominant chorea-acanthocytosis. Neurology 61:
1614-1616, 2003. Note: Erratum: Neurology 77: 701 only, 2011.

29. Sakai, T.; Iwashita, H.; Kakugawa, M.: Neuroacanthocytosis syndrome
and choreoacanthocytosis (Levine-Critchley syndrome). (Letter) Neurology 35:
1679, 1985.

30. Sorrentino, G.; De Renzo, A.; Miniello, S.; Nori, O.; Bonavita,
V.: Late appearance of acanthocytes during the course of chorea-acanthocytosis. J.
Neurol. Sci. 163: 175-178, 1999.

31. Spitz, M. C.; Jankovic, J.; Killian, J. M.: Familial tic disorder,
parkinsonism, motor neuron disease, and acanthocytosis: a new syndrome. Neurology 35:
366-370, 1985.

32. Ueno, S.; Maruki, Y.; Nakamura, M.; Tomemori, Y.; Kamae, K.; Tanabe,
H.; Yamashita, Y.; Matsuda, S.; Kaneko, S.; Sano, A.: The gene encoding
a newly discovered protein, chorein, is mutated in chorea-acanthocytosis. Nature
Genet. 28: 121-122, 2001.

33. Vance, J. M.; Pericak-Vance, M. A.; Bowman, M. H.; Payne, C. S.;
16. Rinne, J. O.; Daniel, S. E.; Scaravilli, F.; Harding, A. E.; Marsden,
C. D.: Nigral degeneration in neuroacanthocytosis. Neurology 44:
1629-1632, 1994.

34. Vance, J. M.; Pericak-Vance, M. A.; Bowman, M. H.; Payne, C. S.;
Fredane, L.; Siddique, T.; Roses, A. D.; Massey, E. W.: Chorea-acanthocytosis:
a report of three new families and implications for genetic counselling. Am.
J. Med. Genet. 28: 403-410, 1987.

35. Villegas, A.; Moscat, J.; Vazquez, A.; Calero, F.; Alvarez-Sala,
J. L.; Artola, S.; Espinos, D.: A new family with hereditary choreo-acanthocytosis. Acta
Haemat. 77: 215-219, 1987.

36. Walker, R. H.; Morgello, S.; Davidoff-Feldman, B.; Melnick, A.;
Walsh, M. J.; Shashidharan, P.; Brin, M. F.: Autosomal dominant chorea-acanthocytosis
with polyglutamine-containing neuronal inclusions. Neurology 58:
1031-1037, 2002.

37. Walker, R. H.; Rasmussen, A.; Rudnicki, D.; Holmes, S. E.; Alonso,
E.; Matsuura, T.; Ashizawa, T.; Davidoff-Feldman, B.; Margolis, R.
L.: Huntington's disease-like 2 can present as chorea-acanthocytosis. Neurology 61:
1002-1004, 2003.

38. Yamamoto, T.; Hirose, G.; Shimazaki, K.; Takado, S.; Kosoegawa,
H.; Sacki, M.: Movement disorder of familial neuroacanthocytosis
syndrome. Arch. Neurol. 39: 298-301, 1982.

*FIELD* CS
INHERITANCE:
Autosomal recessive

HEAD AND NECK:
[Face];
Orofacial dyskinesia;
[Neck];
Neck flexion, intermittent

ABDOMEN:
[Gastrointestinal];
Dysphagia;
Drooling

SKELETAL:
[Feet];
Pes cavus

MUSCLE, SOFT TISSUE:
Limb muscular atrophy;
Limb muscle weakness

NEUROLOGIC:
[Central nervous system];
Progressive choreoathetosis;
Orofacial dyskinesia;
Hyporeflexia;
Dysarthria;
Seizures;
Tics;
Dystonia;
Parkinsonism;
Caudate atrophy;
Putamen atrophy;
Dementia (in some patients);
[Peripheral nervous system];
Hyporeflexia;
Areflexia;
[Behavioral/psychiatric manifestations];
Personality changes;
Mood changes;
Anxiety;
Disinhibition;
Psychosis;
Aggressiveness;
Self-mutilation of tongue and lips due to involuntary movements

HEMATOLOGY:
Acanthocytes

LABORATORY ABNORMALITIES:
Increased creatine kinase;
Normal serum lipoprotein levels

MISCELLANEOUS:
Age of onset 23-59 years;
Clinical variability;
Progressive disorder;
Neurologic findings closely resemble those of Huntington disease (HD,
143100)

MOLECULAR BASIS:
Caused by mutation in the vacuolar protein sorting 13A gene (VPS13A,
605978.0001)

*FIELD* CN
Cassandra L. Kniffin - updated: 11/21/2011
Cassandra L. Kniffin - updated: 11/9/2005
Cassandra L. Kniffin - revised: 1/14/2003

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

*FIELD* ED
joanna: 07/02/2013
joanna: 12/29/2011
joanna: 12/28/2011
ckniffin: 11/21/2011
ckniffin: 11/9/2005
ckniffin: 8/18/2005
ckniffin: 1/14/2003
alopez: 5/30/2001

*FIELD* CN
Cassandra L. Kniffin - updated: 11/21/2011
Cassandra L. Kniffin - updated: 4/10/2008
Jane Kelly - updated: 2/15/2006
Cassandra L. Kniffin - updated: 11/9/2005
Cassandra L. Kniffin - updated: 8/18/2005
Cassandra L. Kniffin - updated: 3/2/2004
Cassandra L. Kniffin - reorganized: 2/25/2004
Victor A. McKusick - updated: 9/3/2002
Victor A. McKusick - updated: 4/3/2002
Victor A. McKusick - updated: 5/24/2001
Victor A. McKusick - updated: 12/8/1999
Victor A. McKusick - updated: 10/17/1997
Orest Hurko - updated: 8/15/1995

*FIELD* CD
Victor A. McKusick: 6/2/1986

*FIELD* ED
carol: 12/09/2013
carol: 1/6/2012
carol: 11/23/2011
ckniffin: 11/21/2011
alopez: 5/2/2011
joanna: 5/7/2009
wwang: 4/16/2008
ckniffin: 4/10/2008
alopez: 2/15/2006
wwang: 11/22/2005
ckniffin: 11/9/2005
wwang: 8/31/2005
wwang: 8/19/2005
ckniffin: 8/18/2005
carol: 3/2/2004
ckniffin: 3/2/2004
carol: 2/25/2004
ckniffin: 2/25/2004
ckniffin: 1/28/2004
carol: 9/18/2002
tkritzer: 9/17/2002
terry: 9/3/2002
terry: 6/3/2002
terry: 4/3/2002
alopez: 5/30/2001
alopez: 5/29/2001
terry: 5/24/2001
carol: 12/8/1999
terry: 12/8/1999
jenny: 10/24/1997
jenny: 10/21/1997
terry: 10/17/1997
alopez: 6/10/1997
mimadm: 11/12/1995
mark: 8/15/1995
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988

MIM 605978
*RECORD*
*FIELD* NO
605978
*FIELD* TI
*605978 VACUOLAR PROTEIN SORTING 13, YEAST, HOMOLOG OF, A; VPS13A
;;CHAC GENE; CHAC;;
read moreCHOREIN;;
KIAA0986
*FIELD* TX

CLONING

In the choreoacanthocytosis (200150) critical region on chromosome 9q,
Rampoldi et al. (2001) identified the VPS13A gene, which they called
CHAC. They identified 2 splice variants: transcript A, which contains
exons 1 to 68 and 70 to 73 and encodes a 3,174-amino acid protein, and
transcript B, which contains exons 1 to 69 and encodes a 3,095-amino
acid protein. Northern blot analysis detected 2 bands of high molecular
mass corresponding to the 2 splice variants in all tissues analyzed.
Additionally, RT-PCR detected expression in the erythrocyte precursor
cell line K562. Rampoldi et al. (2001) showed that the CHAC gene encodes
an evolutionarily conserved protein, which may be involved in protein
sorting.

Independently, Ueno et al. (2001) identified the VPS13A gene and found
that it encodes a 3,096-amino acid protein, which they termed chorein.
Northern blot analysis detected a 10-kb transcript in brain, heart,
skeletal muscle, and kidney.

By EST database analysis and RT-PCR of lymphoid cell line and brain RNA,
Velayos-Baeza et al. (2004) identified several additional splice
variants of VPS13A generated by exon skipping or utilization of
alternative internal exons. Northern blot analysis and RT-PCR detected
VPS13A expression at variable levels in all tissues examined, and
transcript encoding the 3,174-amino acid protein was the major variant.

GENE STRUCTURE

Rampoldi et al. (2001) determined that the VPS13A gene contains 73 exons
and spans 250 kb. Velayos-Baeza et al. (2004) identified 5 additional
alternative exons in the VPS13A gene, exons 7b, 31b, 34b, 68b, and 69b,
but 3 of these, exons 31b, 34b, and 69b, have stop codons in all 3
reading frames.

MAPPING

Rampoldi et al. (2001) mapped the VPS13A gene to chromosome 9q21-q22.
Velayos-Baeza et al. (2004) mapped the mouse Vps13a gene to chromosome
19A.

MOLECULAR GENETICS

In affected members of 11 families with choreoacanthocytosis, Rampoldi
et al. (2001) identified 16 different mutations in the VPS13A gene (see,
e.g., 605978.0001).

In 4 affected patients from 3 Japanese pedigrees with
choreoacanthocytosis, Ueno et al. (2001) identified a homozygous
deletion in the coding region of the VPS13A gene (605978.0003).

Among 43 patients with choreoacanthocytosis, Dobson-Stone et al. (2002)
identified 57 different mutations distributed throughout the CHAC gene
(see, e.g., 605978.0004). In 7 patients, only 1 heterozygous mutation
was found; in 4 patients, no disease mutations were found. The authors
noted that small gene deletions or rearrangements may not have been
detected in these patients.

Dobson-Stone et al. (2005) stated that 75 different mutations in the
VPS13A gene had been identified in 58 probands with
choreoacanthocytosis.

*FIELD* AV
.0001
CHOREOACANTHOCYTOSIS
VPS13A, ILE90LYS

In a patient with choreoacanthocytosis (200150), Rampoldi et al. (2001)
found compound heterozygosity for a 269T-A transversion in exon 4 of the
VPS13A gene and an insertion of a T between nucleotides 6404 and 6405 in
exon 48. The mutations resulted in an ile90-to-lys (I90K) amino acid
change and a frameshift, respectively.

.0002
CHOREOACANTHOCYTOSIS
VPS13A, 1-BP INS, 6404T

See 605978.0001 and Rampoldi et al. (2001).

.0003
CHOREOACANTHOCYTOSIS
VPS13A, 260-BP DEL

In affected members of 3 Japanese families with choreoacanthocytosis
(200150), Ueno et al. (2001) identified a homozygous 260-bp deletion in
the VPS13A gene, leading to a truncated protein. The families originated
from a small area in Japan, and haplotype analysis indicated a founder
effect. Some of the patients' parents, who were heterozygous for the
mutation, showed a slight degree of acanthocytosis in peripheral blood
but no distinct neurologic abnormalities except for cryptogenic abducens
palsy in 1 parent.

.0004
CHOREOACANTHOCYTOSIS
VPS13A, ARG208TER

In 3 patients with choreoacanthocytosis, Dobson-Stone et al. (2002)
identified a 622C-T change in exon 9 of the CHAC gene, resulting in an
arg208-to-ter nonsense substitution (R208X). One patient was homozygous
for the mutation and 2 others were compound heterozygous for R208X and
another CHAC mutation. The R208X mutation had previously been reported
by Rampoldi et al. (2001) in a family with choreoacanthocytosis.

.0005
CHOREOACANTHOCYTOSIS
VPS13A, 8035G-A

In 2 affected sibs from a Japanese family with choreoacanthocytosis
(200150) with apparent autosomal dominant inheritance, Saiki et al.
(2003) identified a heterozygous G-to-A transversion at the last
nucleotide of exon 57 of the CHAC gene, predicted to induce skipping of
exon 57 and premature termination of the protein. The mutation was not
detected in their unaffected mother. Family history revealed that 3
other living family members were affected and 2 deceased members were
believed to be affected. All 5 living affected members showed
acanthocytosis (approximately 15-20%) and involuntary movements. In an
erratum, the authors stated that an error in sequencing had occurred and
the inheritance pattern should have been reported as autosomal recessive
(pseudodominant). Tomiyasu et al. (2011) identified the 2 mutations in
the VPS13A gene in this family: an 8035G-A transition in exon 57,
causing a frameshift and premature termination (Ile2652HisfsTer12), and
a 1305G-A transition in exon 15, resulting in a trp435-to-ter (W435X;
605978.0010) substitution; the latter mutation was also identified in
the unaffected mother.

.0006
CHOREOACANTHOCYTOSIS
VPS13A, 1-BP DEL, 6059C

In 2 unrelated males of Ashkenazi Jewish descent with
choreoacanthocytosis (200150), Lossos et al. (2005) identified a
homozygous 1-bp deletion (6059delC) in exon 46 of the VPS13A gene,
predicted to result in premature termination of the protein.

.0007
CHOREOACANTHOCYTOSIS
VPS13A, 7-KB DEL

In an Iraqi Jewish woman with choreoacanthocytosis (200150), Lossos et
al. (2005) identified a homozygous 7-kb deletion spanning exon 23 of the
VPS13A gene. She had trichotillomania and anxiety but little
neuromuscular involvement.

.0008
CHOREOACANTHOCYTOSIS
VPS13A, 37-KB DEL

In affected members of 3 French Canadian families with
choreoacanthocytosis (200150), Dobson-Stone et al. (2005) identified a
homozygous 37-kb deletion in the VPS13A gene, resulting in the deletion
of exons 70 through 73. The deletion also encompassed the 2 terminal
exons of the neighboring GNA14 gene (604397). Haplotype analysis
indicated a founder effect.

.0009
CHOREOACANTHOCYTOSIS
VPS13A, 2-BP DUP, 3556AC

In 2 Mexican mestizo sisters, born of consanguineous parents, with
choreoacanthocytosis (200150), Ruiz-Sandoval et al. (2007) identified a
homozygous 2-bp duplication (3556dupAC) in exon 33 of the VPS13A gene,
resulting in a frameshift and premature termination. The proband had
onset at age 32 years and showed severe progression of the disorder; at
age 42, she was emaciated, anarthric, and reactive only to simple
commands. In contrast, her sister had onset at age 45 years and
primarily showed motor and verbal tics, paranoid behavior, and
depression.

.0010
CHOREOACANTHOCYTOSIS
VPS13A, TRP435TER

See 605978.0005 and Tomiyasu et al. (2011).

*FIELD* RF
1. Dobson-Stone, C.; Danek, A.; Rampoldi, L.; Hardie, R. J.; Chalmers,
R. M.; Wood, N. W.; Bohlega, S.; Dotti, M. T.; Federico, A.; Shizuka,
M.; Tanaka, M.; Watanabe, M.; and 32 others: Mutational spectrum
of the CHAC gene in patients with chorea-acanthocytosis. Europ. J.
Hum. Genet. 10: 773-781, 2002.

2. Dobson-Stone, C.; Velayos-Baeza, A.; Jansen, A.; Andermann, F.;
Dubeau, F.; Robert, F.; Summers, A.; Lang, A. E.; Chouinard, S.; Danek,
A.; Andermann, E.; Monaco, A. P.: Identification of a VPS13A founder
mutation in French Canadian families with chorea-acanthocytosis. Neurogenetics 6:
151-158, 2005.

3. Lossos, A.; Dobson-Stone, C.; Monaco, A. P.; Soffer, D.; Rahamim,
E.; Newman, J. P.; Mohiddin, S.; Fananapazir, L.; Lerer, I.; Linetsky,
E.; Reches, A.; Argov, Z.; Abramsky, O.; Gadoth, N.; Sadeh, M.; Gomori,
J. M.; Boher, M.; Meiner, V.: Early clinical heterogeneity in choreoacanthocytosis. Arch.
Neurol. 62: 611-614, 2005.

4. Rampoldi, L.; Dobson-Stone, C.; Rubio, J. P.; Danek, A.; Chalmers,
R. M.; Wood, N. W.; Verellen, C.; Ferrer, X.; Malandrini, A.; Fabrizi,
G. M.; Brown, R.; Vance, J.; Pericak-Vance, M.; Rudolf, G.; Carre,
S.; Alonso, E.; Manfredi, M.; Nemeth, A. H.; Monaco, A. P.: A conserved
sorting-associated protein is mutant in chorea-acanthocytosis. Nature
Genet. 28: 119-120, 2001.

5. Ruiz-Sandoval, J. L.; Garcia-Navarro, V.; Chiquete, E.; Dobson-Stone,
C.; Monaco, A. P.; Alvarez-Palazuelos, L. E.; Padilla-Martinez, J.
J.; Barrera-Chairez, E.; Rodriguez-Figueroa, E. I.; Perez-Garcia,
G.: Choreoacanthocytosis in a Mexican family. Arch. Neurol. 64:
1661-1664, 2007.

6. Saiki, S.; Sakai, K.; Kitagawa, Y.; Saiki, M.; Kataoka, S.; Hirose,
G.: Mutation in the CHAC gene in a family of autosomal dominant chorea-acanthocytosis. Neurology 61:
1614-1616, 2003. Note: Erratum: Neurology 77: 701 only, 2011.

7. Tomiyasu, A.; Nakamura, M.; Ichiba, M.; Ueno, S.; Saiki, S.; Morimoto,
M.; Kobal, J.; Kageyama, Y.; Inui, T.; Wakabayashi, K.; Yamada, T.;
Kanemori, Y.; and 22 others: Novel pathogenic mutations and copy
number variations in the VPS13A gene in patients with chorea-acanthocytosis. Am.
J. Med. Genet. (Neuropsychiat. Genet.) 156B: 620-631, 2011.

8. Ueno, S.; Maruki, Y.; Nakamura, M.; Tomemori, Y.; Kamae, K.; Tanabe,
H.; Yamashita, Y.; Matsuda, S.; Kaneko, S.; Sano, A.: The gene encoding
a newly discovered protein, chorein, is mutated in chorea-acanthocytosis. Nature
Genet. 28: 121-122, 2001.

9. Velayos-Baeza, A.; Vettori, A.; Copley, R. R.; Dobson-Stone, C.;
Monaco, A. P.: Analysis of the human VPS13 gene family. Genomics 84:
536-549, 2004.

*FIELD* CN
Carol A. Bocchini - updated: 10/1/2012
Cassandra L. Kniffin - updated: 4/10/2008
Cassandra L. Kniffin - updated: 11/9/2005
Cassandra L. Kniffin - updated: 8/18/2005
Patricia A. Hartz - updated: 8/26/2004
Cassandra L. Kniffin - updated: 3/2/2004

*FIELD* CD
Victor A. McKusick: 5/29/2001

*FIELD* ED
carol: 09/06/2013
terry: 10/2/2012
terry: 10/1/2012
carol: 10/1/2012
carol: 1/6/2012
wwang: 4/16/2008
ckniffin: 4/10/2008
wwang: 11/22/2005
ckniffin: 11/9/2005
wwang: 8/19/2005
ckniffin: 8/18/2005
mgross: 8/27/2004
terry: 8/26/2004
mgross: 3/25/2004
carol: 3/2/2004
ckniffin: 3/2/2004
carol: 2/25/2004
ckniffin: 2/3/2004
alopez: 5/29/2001