Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

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