Origin of the Spinocerebellar Ataxia Type 7 (Sca7) Mutations in the Spanish Population: Evidence for a Founder Effect

Abstract Background Spinocerebellar ataxia type 7 is a rare, progressive, autosomal dominant neurodegenerative disorder caused by a pathogenic CAG repeat expansion in exon 3 of the ATXN7 gene, characterized by cerebellar ataxia and retinal degeneration. Its prevalence varies markedly across geographical regions, which suggests potential founder effects. Objective to investigate the origin of pathogenic spinocerebellar ataxia type 7 expansions in Spain by a comprehensive clinical and genetic overview of a cohort of 12 Spanish families. Methods the cohort was clinically described and the patients were selected and molecular genotyped using a dual approach involving direct triplet repeat-primed PCR analysis or bioinformatics screening of Next Generation Sequencing data. Haplotypes were constructed using four microsatellite markers and one intragenic SNP. Statistical analyses were conducted using R software. Results reveal high phenotypic heterogeneity of spinocerebellar ataxia type 7, with and age of onset and expansion sizes (35 to > 100 repeats) varying widely. Haplotype analysis identified a common allele among eight individuals from five unrelated families in the same geographical area, as well as one patient from a different region. Conclusion these findings strongly support the existence of a founder effect for spinocerebellar ataxia type 7 within the Spanish population.