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.
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Acknowledgements
We thank the patients for cooperation; L.P.W. Ranum for confirming RED analysis results; and The Sanger Centre for BAC, PAC and cosmid clones located in the chromosome 22 region of interest. This work was supported by grants from the Oxnard Foundation/National Ataxia Foundation (T.A.), National Ataxia Foundation (S.M.P.), Howard Hughes Medical Institute (H.Y.Z.), the National Institute of Health/NICHD HD29256 (D.L.N.), MRRC HD24064, NINDS NS27699 and GCRCM01RR00188 (H.Y.Z.), NS29709 (J.L.N.), NS33123 and NS37883 (S.M.P.), and K12-AG0052-01 (R.P.G.). The fellowship of T.M. was partly supported by the Cell Science Research Foundation, the Yamanouchi Foundation for Research on Metabolic Disorders and the Nakayama Foundation for Human Science, Japan. D.L.B. was supported by an American Epilepsy Society Fellowship.
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Matsuura, T., Yamagata, T., Burgess, D. et al. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 26, 191–194 (2000). https://doi.org/10.1038/79911
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DOI: https://doi.org/10.1038/79911
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