학술논문
Genotype–phenotype correlation in PRKN-associated Parkinson’s disease
Document Type
article
Author
Poornima Jayadev Menon; Sara Sambin; Baptiste Criniere-Boizet; Thomas Courtin; Christelle Tesson; Fanny Casse; Melanie Ferrien; Louise-Laure Mariani; Stephanie Carvalho; Francois-Xavier Lejeune; Sana Rebbah; Gaspard Martet; Marion Houot; Aymeric Lanore; Graziella Mangone; Emmanuel Roze; Marie Vidailhet; Jan Aasly; Ziv Gan Or; Eric Yu; Yves Dauvilliers; Alexander Zimprich; Volker Tomantschger; Walter Pirker; Ignacio Álvarez; Pau Pastor; Alessio Di Fonzo; Kailash P. Bhatia; Francesca Magrinelli; Henry Houlden; Raquel Real; Andrea Quattrone; Patricia Limousin; Prasad Korlipara; Thomas Foltynie; Donald Grosset; Nigel Williams; Derek Narendra; Hsin-Pin Lin; Carna Jovanovic; Marina Svetel; Timothy Lynch; Amy Gallagher; Wim Vandenberghe; Thomas Gasser; Kathrin Brockmann; Huw R. Morris; Max Borsche; Christine Klein; Olga Corti; Alexis Brice; Suzanne Lesage; Jean Christophe Corvol; French Parkinson disease Genetics Study Group (PDG)
Source
npj Parkinson's Disease, Vol 10, Iss 1, Pp 1-12 (2024)
Subject
Language
English
ISSN
2373-8057
Abstract
Abstract Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p