Reduced penetrance of intermediate size alleles in spinocerebellar ataxia type 10

Triplet repeat expansions are the disease-causing mutations in nine dominantly inherited spinocerebellar ataxias (SCAs).1 In 2000, a new type of dynamic mutation was reported in Mexican patients with SCA and seizures, consisting of a (ATTCT)n expansion found in intron 9 of the SCA10 gene2; normal alleles have 10 to 29 and pathologic 800 to 4,500 repeats. We studied 329 unrelated SCA patients. Ataxia was sometimes associated with other features, such as epilepsy, mental retardation, seizures, paraplegia, or tremor; 290 were Portuguese, 39 were from Brazil. Peripheral blood was collected from patients and their relatives, after written informed consent. The (ATTCT)n was amplified by PCR with flanking primers and Southern blot was performed as described elsewhere.2,3 The modified PCR analysis for (ATTCT)n expansion showed that three patients (figure, A and B), from two unrelated Brazilian families, with an admixture of Portuguese and Amerindian ancestry, had a continuous ladder exceeding the product range observed for normal alleles at the SCA10 locus. These patients had first shown a single band after PCR for normal allele sizing (figure, C). Expansion size assessment (figure, D) identified one allele with 400 repeats in Patient II-2 …