Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10

Tohru Matsuura, Takanori Yamagata, Daniel L. Burgess, Astrid Rasmussen, Raji P. Grewal, Kei Watase, Mehrdad Khajavi, Alanna E. McCall, Caleb F. Davis, Lan Zu, Madhureeta Achari, Stefan M. Pulst, Elisa Alonso, Jeffrey L. Noebels, David L. Nelson, Huda Y. Zoghbi, Tetsuo Ashizawa

Research output: Contribution to journalArticlepeer-review

440 Scopus citations

Abstract

Spinocerebellar ataxia type 10 (SCA10 MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

Original languageEnglish (US)
Pages (from-to)191-194
Number of pages4
JournalNature Genetics
Volume26
Issue number2
DOIs
StatePublished - Oct 2000

ASJC Scopus subject areas

  • Genetics

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