Biallelic expansion in RFC1 as a rare cause of Parkinson\u2019s disease

Laura Kytövuori,Kari Majamaa,Eriko Koshimizu,Hiroshi Doi,Naomichi Matsumoto,Ari Siitonen,Jussi Sipilä,Satoko Miyatake,Anri Hurme-Niiranen,Fumiaki Tanaka

doi:10.1038/s41531-021-00275-7

Abstract

An intronic expansion (AAGGG)exp in the RFC1 gene has recently been shown to cause recessively inherited cerebellar ataxia, neuropathy, and vestibular areflexia syndrome and, furthermore, a few patients with ataxia and parkinsonism have been reported. We investigated 569 Finnish patients with medicated parkinsonism for RFC1 and found biallelic (AAGGG)exp in three non-consanguineous patients with clinically confirmed Parkinson’s disease without ataxia suggesting that RFC1-related disorders include Parkinson’s disease as well.

Highlights

The replication factor C complex is a five-subunit ATPase required for DNA replication and repair
We report on screening of a population-based cohort of Finnish patients with medicated parkinsonism for RFC1 (AAGGG)exp
We found nine subjects with the homozygous (AAGGG)expassociated core haplotype among 569 patients with medicated parkinsonism (Supplementary Table 1) and two out of 269 controls

Summary

Introduction

The replication factor C complex is a five-subunit ATPase required for DNA replication and repair. We report on screening of a population-based cohort of Finnish patients with medicated parkinsonism for RFC1 (AAGGG)exp. We found nine subjects with the homozygous (AAGGG)expassociated core haplotype among 569 patients with medicated parkinsonism (Supplementary Table 1) and two out of 269 controls. But three of the 9 patients, harbored biallelic (AAGGG)exp in RFC1 (Fig. 1).

Results

Conclusion