Spinocerebellar ataxia type 10 (
SCA10), an autosomal dominant
neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the
Ataxin 10 gene.
SCA10 patients present with pure
cerebellar ataxia; yet, some families also have a high incidence of
epilepsy.
SCA10 expansions containing
penta- and heptanucleotide interruption motifs, termed "ATCCT interruptions," experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of
genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic
seizures in one Mexican-American
SCA10 family. In a large cohort of
SCA10 families, we analyzed whether ATCCT interruptions confer a greater risk for developing
seizures in these families. Notably, we find that the presence of repeat interruptions within the
SCA10 expansion confers a 6.3-fold increase in the risk of an
SCA10 patient developing
epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of
epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in
SCA10 repeat expansion indicates a significant risk for the
epilepsy phenotype and should be considered during genetic counseling.