Inter-generational instability of inserted repeats during transmission in spinocerebellar ataxia type 31

摘要

The causative mutation for spinocerebellar ataxia type 31 (SCA31) is an intronic insertion containing pathogenic pentanucleotide repeats, (TGGAA)(n). We examined to what degree the inserted repeats were unstable during transmission. In 14 parent-child pairs, the average change of onset age was -6.4 +/- 7.3 years (mean +/- s.d.) in the child generation when compared with the parent generation. Of the 11 pairs analyzed, six showed expansion of inserted repeat length during transmission, and five showed contraction. On average, the inserted repeats expanded by 12.2 +/- 32.7 bp during transmission, but their mean length (with a 95% confidence interval) was not significantly different between parent and child generations. We consider that the length of the inserted repeats in SCA31 is changeable during transmission, but inter-generational instability is not marked, as far as the current sizing method can determine.