Curation SCA10 ATXN10

Six unrelated SCA10 families were analyzed (three Brazilian, two Mexican mapping families, and one early-onset Mexican patient), comprising 34 SCA10 expansion carriers and 20 relatives with cerebellar ataxia and variable seizures.

An inverse correlation has been observed between the expansion size and the age of onset (r2=0.34, P=0.018).

A four-generation Mexican-American autosomal dominant SCA pedigree showed linkage to chromosome 22q13, with maximum two-point LOD score 4.30 at D22S928 and D22S1161 (θ=0) and informative haplotypes defining recombination events.

SCA10 expanded chromosomes shared conserved intragenic/flanking haplotypes; 154 control chromosomes from Brazilian, Mexican, and Portuguese populations were analyzed for haplotype frequencies and showed low-frequency disease-associated flanking haplotypes.

pmid:11017075 notes that the large intronic ATTCT expansion could affect ATXN10 transcription or post-transcriptional processing, but preliminary northern blot data showed no obvious SCA10 mRNA change in patient lymphoblastoid cells; pmid:38467784 provides review-level context that STR sequence composition can affect gene expression.

Patient lymphoblastoid cells were used for western blotting to exclude expanded polyglutamine proteins and for preliminary northern blot analysis showing no obvious SCA10 mRNA level change; disease-relevant patient-cell functional alteration was not demonstrated.