ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.
Nat Genet
; 24(2): 120-5, 2000 Feb.
Article
em En
| MEDLINE
| ID: mdl-10655055
ABSTRACT
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ataxia
/
Cromossomos Humanos Par 13
/
Degenerações Espinocerebelares
/
Fases de Leitura Aberta
/
Proteínas de Choque Térmico
/
Mutação
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article