Long-read sequencing revealed complex biallelic pentanucleotide repeat expansions in RFC1-related Parkinson's disease.

ABSTRACT: Biallelic intronic pentanucleotide repeat expansions, mainly (AAGGG)exp and/or (ACAGG)exp in RFC1, are detected in cerebellar ataxia, neuropathy and vestibular areflexia syndrome, late-onset ataxia, and in a wide disease spectrum including Charcot-Marie-Tooth disease, multiple system atrophy, and Parkinson's disease (PD). However, the genotype-phenotype correlation and underlying mechanism are mostly unknown. We screened RFC1-repeat expansions in 1445 patients with parkinsonism. Comprehensive genetic and clinical, and pathological assessments were performed. We report two early-onset patients with PD carrying complex biallelic pentanucleotide repeat expansions in RFC1. Long-read sequencing revealed a novel repeat configuration of (AGGGG)exp(AAGGG)₁₄ and a possible somatic varian

SUBMITTER: Liu P 

PROVIDER: S-EPMC11747075 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature