Profiling Complex Repeat Expansions in RFC1 in Parkinson’s Disease

Authors

Pilar Alvarez Jerez
Kensuke Daida
Abigail Miano-Burkhardt
Hirotaka Iwaki
Laksh Malik
Guillaume Cogan
Mary B Makarious
Roisin Sullivan
Jana Vandrovcova
Jinhui Ding
J Raphael Gibbs
Androo Markham
Mike A Nalls
Rupesh K Kesharwani
Fritz J Sedlazeck
Bradford Casey
John Hardy
Henry Houlden
Cornelis Blauwendraat
Andrew B Singleton
Kimberley J Billingsley

Publication Date

5-24-2024

Journal

Npj Parkinson's Journal

DOI

10.1038/s41531-024-00723-0

PMID

38789445

PMCID

PMC11126591

PubMedCentral® Posted Date

5-24-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Structural variation, DNA sequencing

Abstract

A biallelic (AAGGG) expansion in the poly(A) tail of an AluSx3 transposable element within the gene RFC1 is a frequent cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), and more recently, has been reported as a rare cause of Parkinson's disease (PD) in the Finnish population. Here, we investigate the prevalence of RFC1 (AAGGG) expansions in PD patients of non-Finnish European ancestry in 1609 individuals from the Parkinson's Progression Markers Initiative study. We identified four PD patients carrying the biallelic RFC1 (AAGGG) expansion and did not identify any carriers in controls.