Mutation Analysis of DNAJC Family for Early-Onset Parkinson's Disease in a Chinese Cohort.
DNAJCs
early-onset Parkinson's disease
genetics
mutation
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
11
02
2020
revised:
30
05
2020
accepted:
17
06
2020
pubmed:
15
7
2020
medline:
28
4
2021
entrez:
15
7
2020
Statut:
ppublish
Résumé
Recently, members of the DnaJ homolog C (DNAJC) family have been identified to be associated with Parkinson's disease (PD) and other neurodegenerative disorders. However, most studies are based on European-ancestry population and no comprehensive analysis is further conducted. In this study, we aim to systematically explore the associations of DNAJCs by genetic analysis in a large Chinese early-onset PD (EOPD) cohort. Rare variants were identified using whole exome sequencing in a cohort of 664 unrelated patients with EOPD. Allelic association analysis was performed with Fisher's exact test to clarify the associations at allele level. Gene-based burden analysis was conducted for both rare variants and damaging variants to illuminate the involvement of DNAJCs in EOPD at the gene level. In total, 61 rare variants were identified in the current study. At the allele level, 2 variants, p.T1109R and p.L174H, in DNAJC26 were significant after Bonferroni correction; 2 variants, p.V1271A and p.A476V, in DNAJC26; 2 variants, p.M477T and p.D1670G, in DNAJC13; 1 variant, p.L19I, in DNAJC10; and 1 variant, p.N526S, in DNAJC6 reached nominal significance. Moreover, a novel compound heterozygous mutation in DNAJC6 was identified. At the gene level, gene-based burden analysis showed a clear enrichment of rare variants in DNAJC26 in patients with EOPD, but not other DNAJCs. Our work identifies novel rare variants of DNAJC26 to be associated with EOPD and enhances our understanding of the role of DNAJC family members in EOPD. © 2020 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Recently, members of the DnaJ homolog C (DNAJC) family have been identified to be associated with Parkinson's disease (PD) and other neurodegenerative disorders. However, most studies are based on European-ancestry population and no comprehensive analysis is further conducted.
OBJECTIVES
In this study, we aim to systematically explore the associations of DNAJCs by genetic analysis in a large Chinese early-onset PD (EOPD) cohort.
METHODS
Rare variants were identified using whole exome sequencing in a cohort of 664 unrelated patients with EOPD. Allelic association analysis was performed with Fisher's exact test to clarify the associations at allele level. Gene-based burden analysis was conducted for both rare variants and damaging variants to illuminate the involvement of DNAJCs in EOPD at the gene level.
RESULTS
In total, 61 rare variants were identified in the current study. At the allele level, 2 variants, p.T1109R and p.L174H, in DNAJC26 were significant after Bonferroni correction; 2 variants, p.V1271A and p.A476V, in DNAJC26; 2 variants, p.M477T and p.D1670G, in DNAJC13; 1 variant, p.L19I, in DNAJC10; and 1 variant, p.N526S, in DNAJC6 reached nominal significance. Moreover, a novel compound heterozygous mutation in DNAJC6 was identified. At the gene level, gene-based burden analysis showed a clear enrichment of rare variants in DNAJC26 in patients with EOPD, but not other DNAJCs.
CONCLUSIONS
Our work identifies novel rare variants of DNAJC26 to be associated with EOPD and enhances our understanding of the role of DNAJC family members in EOPD. © 2020 International Parkinson and Movement Disorder Society.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2068-2076Informations de copyright
© 2020 International Parkinson and Movement Disorder Society.
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