Somatic instability of the FGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum.

ABSTRACT: Spinocerebellar ataxia 27B (SCA27B) is a common autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. Neuropathological studies have shown that neuronal loss is largely restricted to the cerebellum. Although the repeat locus is highly unstable during intergenerational transmission, it remains unknown whether it exhibits cerebral mosaicism and progressive instability throughout life. We conducted an analysis of the FGF14 GAA•TTC repeat somatic instability across 156 serial blood samples from 69 individuals, fibroblasts, induced pluripotent stem cells and post-mortem brain tissues from six controls and six patients with SCA27B, alongside methylation profiling using targeted long-read sequencing. Peripheral tissues exhibited minimal somatic instability, which did

SUBMITTER: Pellerin D 

PROVIDER: S-EPMC11969470 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature