Profiling complex repeat expansions in RFC1 in Parkinson's disease

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

doi:10.1038/s41531-024-00723-0

Profiling complex repeat expansions in RFC1 in Parkinson's disease

NPJ Parkinsons Dis. 2024 May 24;10(1):108. doi: 10.1038/s41531-024-00723-0.

Authors

Pilar Alvarez Jerez^{1

2

3}, Kensuke Daida^{1

2}, Abigail Miano-Burkhardt^{1

2}, Hirotaka Iwaki^{1

2

4}, Laksh Malik², Guillaume Cogan^{1

5}, Mary B Makarious^{1

6}, Roisin Sullivan⁷, Jana Vandrovcova⁷, Jinhui Ding¹, J Raphael Gibbs¹, Androo Markham⁸, Mike A Nalls^{1

2

4}, Rupesh K Kesharwani⁹, Fritz J Sedlazeck^{9

10

11}, Bradford Casey¹², John Hardy³, Henry Houlden^{6

7}, Cornelis Blauwendraat^{1

2}, Andrew B Singleton^{1

2}, Kimberley J Billingsley^{13

14}

Affiliations

¹ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
² Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD, USA.
³ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁴ DataTecnica LLC, Washington, DC, USA.
⁵ Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Institut National de la Recherche Médicale-U1127, Centre National de la Recherche Scientifique, Paris, France.
⁶ UCL Movement Disorders Centre, University College London, London, UK.
⁷ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
⁸ Oxford Nanopore Technologies, Oxford, UK.
⁹ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
¹⁰ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
¹¹ Department of Computer Science, Rice University, Houston, TX, USA.
¹² The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
¹³ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA. kimberley.billingsley@nih.gov.
¹⁴ Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD, USA. kimberley.billingsley@nih.gov.

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.