Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

A systematic screening to identifyde novomutations causing sporadic early-onset Parkinson's disease

Kun-Rodrigues, Celia, Ganos, Christos, Guerreiro, Rita, Schneider, Susanne A., Schulte, Claudia, Lesage, Suzanne, Darwent, Lee, Holmans, Peter Alan ORCID:, Singleton, Andrew, Bhatia, Kailash and Bras, Jose 2015. A systematic screening to identifyde novomutations causing sporadic early-onset Parkinson's disease. Human Molecular Genetics 24 (23) , pp. 6711-20. 10.1093/hmg/ddv376

[thumbnail of ddv376.pdf]
PDF - Published Version
Available under License Creative Commons Attribution.

Download (478kB) | Preview


Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent-child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein-protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Oxford University Press
ISSN: 0964-6906
Date of First Compliant Deposit: 16 September 2019
Date of Acceptance: 8 September 2015
Last Modified: 31 Oct 2022 09:24

Citation Data

Cited 29 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics