A conserved sorting-associated protein is mutant in chorea-acanthocytosis

Rampoldi, Luca; Dobson‐Stone, Carol; Rubio, Justin P.; Danek, Adrian; Chalmers, R. M.; Wood, Nicholas W.; Verellen, Christine; Ferrer, Xavier; Malandrini, Alessandro; Fabrizi, Gian Maria; Brown, Robert H.; Vance, Jeffery M.; Pericak‐Vance, Margaret A.; Rudolf, Gabrielle; Carré, Sophie; Alonso, Elisa; Manfredi, M.; Németh, Andrea H.; Monaco, Anthony P.

doi:10.1038/88821

Cited by 321 publications

(248 citation statements)

References 11 publications

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“…Only three of these mutations have been previously reported, in other families. 11 All available family members were screened for the relevant mutation(s) using the verification method outlined in Table 1; in each case, the mutation(s) co-segregated consistently with the affection status. In seven patients only one heterozygous mutation was found; in four patients with typical symptoms of ChAc, no disease mutations were found.…”

Section: Resultsmentioning

confidence: 99%

“…Probands 12 and 39 are heterozygous and proband 27 is homozygous for the mutation R208X, which was also found in family CHAC3 reported earlier. 11 Probands 1 and 34 have mutations (R3037X and 9429_9432del, respectively) that had initially been identified in families CHAC7 and CHAC11. 11 As we could not perform haplotype analysis on certain probands in this study, it is not possible to determine whether they are related.…”

Section: Discussionmentioning

confidence: 99%

“…11 Probands 1 and 34 have mutations (R3037X and 9429_9432del, respectively) that had initially been identified in families CHAC7 and CHAC11. 11 As we could not perform haplotype analysis on certain probands in this study, it is not possible to determine whether they are related. Family CHAC3 and proband 12 both originate from Italy and so it is conceivable that their mutation was inherited from a common ancestor.…”

Section: Discussionmentioning

confidence: 99%

“…10 We subsequently identified a novel gene in the ChAc critical region and found 16 different mutations in these same 11 families. 11 Another group who independently identified the gene reported one other mutation in three Japanese families. 12 The CHAC gene is organised in 73 exons spanning about 250 kb of the genome.…”

Section: Introductionmentioning

confidence: 99%

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Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis

Dobson‐Stone

Danek

Rampoldi³

et al. 2002

Eur J Hum Genet

144

123

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Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/ deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis

Dobson‐Stone

Danek

Rampoldi³

et al. 2002

Eur J Hum Genet

144

123

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“…This symptom variation in presentation is responsible for the under diagnosis of this clinical entity. Chorea acanthocytosis is caused by mutation of 73 exon gene on chromosome 9, VPS13A which codes for Chorein [1].…”

Section: Discussionmentioning

confidence: 99%

Feeding dystonia: A classical presentation of neuroacanthocytosis

Kushwaha¹,

Panda²,

Mehta³

et al. 2013

IJCRI

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Early Clinical Heterogeneity in Choreoacanthocytosis

Lossos¹,

Dobson‐Stone²,

Monaco³

et al. 2005

Arch Neurol

Self Cite

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Background: Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. Objective: To describe the early clinical features and possible genotype-phenotype correlation in CHAC. Design and Setting: Case series in a tertiary care center. Patients and Main Outcome Methods: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A. Results: Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. Conclusions: These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.

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A conserved sorting-associated protein is mutant in chorea-acanthocytosis

Cited by 321 publications

References 11 publications

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis

Feeding dystonia: A classical presentation of neuroacanthocytosis

Early Clinical Heterogeneity in Choreoacanthocytosis

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