title: Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures.
abstract: 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.
authors: Department of Neurology, University of Florida, Gainesville, FL, 32610, USA.
authors: Karen N
authors: KN
authors: McFarland
authors: Jilin
authors: J
authors: Liu
authors: Ivette
authors: I
authors: Landrian
authors: Desmond
authors: D
authors: Zeng
authors: Salmo
authors: S
authors: Raskin
authors: Mariana
authors: M
authors: Moscovich
authors: Emilia M
authors: EM
authors: Gatto
authors: Adriana
authors: A
authors: Ochoa
authors: Hélio A G
authors: HA
authors: Teive
authors: Astrid
authors: A
authors: Rasmussen
authors: Tetsuo
authors: T
authors: Ashizawa
mesh_terms: D000328:Adult; D000483:Alleles; D016000:Cluster Analysis; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics; D004827:Epilepsy / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D008800:Mexico; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D012306:Risk; D017422:Sequence Analysis, DNA; D020754:Spinocerebellar Ataxias / Q000235:genetics*