Spinocerebellar Ataxia Type 10: Haplotype Analyses in 15 Brazilian and Peruvian Families (P05.044)

OBJECTIVE: To identify a previously described haplotype, shared by 3 SCA10 Brazilian families, in additional patients from Brazil and new cases from Peru. BACKGROUND: Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative disease characterized by cerebellar ataxia and seizures, and inherited as an autosomal dominant trait. A large expansion of a pentanucleotide repeat (ATTCT) in intron 9 of the ATXN10 gene is the molecular basis of this disease. To date, SCA10 was described in patients from Latin-America countries only. A common Amerindian ethnic origin of SCA10 families, together with lack of SCA10 cases in European countries, supports a local founder effect for a SCA10 mutation. DESIGN/METHODS: Haplotype analysis was performed based on polymorphic markers within and flanking the ATXN10 gene in 23 confirmed SCA10 cases: 3 families have been describe previously (Alonso et al, 2006; Almeida et al, 2009), while 12 families were newly identified, within a large cohort of patients with ataxia. From those, 3 families were from Peru, while the remaining 9 were from Brazil (clinical description is reported separately). The same polymorphic markers and haplotypes were typed in 100 individuals (200 alleles) from the general local population. RESULTS: A different haplotype distribution was found in SCA10 patients and the control group. The most frequent haplotype was the same in both groups; however, frequencies were considerably different. This haplotype was found in 12 from the total of 15 families, being present in 20 out of 23 patients with expanded alleles in the ATXN10 gene. CONCLUSIONS: Additional cases of SCA10 from Brazil and from Peru confirm the presence of a consistently recurrent haplotype that suggests a common ancestry for the vast majority of SCA10 patients. We are aware that other haplotypes can also be found segregating with the nucleotide expansion in the ATXN10 gene, but at much lower frequency. Supported by: CNPq, FIPE-HCPA, FAPERGS, INAGEMP, RIBERMOV. Disclosure: Dr. Saraiva-Pereira has nothing to disclose. Dr. Gheno has nothing to disclose. Dr. Furtado has nothing to disclose. Dr. Saute has nothing to disclose. Dr. Donis has nothing to disclose. Dr. Fontanari has nothing to disclose. Dr. Emmel has nothing to disclose. Dr. Pedroso has nothing to disclose. Dr. Barsottini has nothing to disclose. Dr. Godeiro-Junior has nothing to disclose. Dr. van der Linden has nothing to disclose. Dr. Pereira has nothing to disclose. Dr. Castilhos has nothing to disclose. Dr. Alonso has nothing to disclose. Dr. Sequeiros has nothing to disclose. Dr. Cornejo has received personal compensation for activities with Schwartz. Dr. Cornejo has received research support from Vanderbilt University. Dr. Mazzetti has received personal compensation for activities with Novartis, Eli Lilly, and Schwartz. Dr. Torman has nothing to disclose. Dr. Jardim has nothing to disclose.