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The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.
- Source :
-
Clinical genetics [Clin Genet] 2018 Oct; Vol. 94 (3-4), pp. 339-345. Date of Electronic Publication: 2018 Jul 16. - Publication Year :
- 2018
-
Abstract
- Biallelic GBA mutations cause Gaucher disease (GD), and heterozygous carriers are at risk for synucleinopathies. No founder GBA mutations in French-Canadians are known. GBA was fully sequenced using targeted next generation and Sanger sequencing in French-Canadian Parkinson disease (PD) patients (n = 436), rapid eye movement (REM)-sleep behavior disorder (RBD) patients (n = 189) and controls (n = 891). Haplotype, identity-by-descent (IBD) and principal component analyses (PCA) were performed using single nucleotide polymorphism-chip data. Data on GD patients from Toronto and Montreal were collected from patients' files. A GBA p.Trp378Gly mutation was identified in two RBD and four PD patients (1% of all patients combined), and not in controls. The two RBD patients had converted to DLB within 3 years of their diagnosis. Haplotype, IBD and PCA analysis demonstrated that this mutation is from a single founder. Out of 167 GD patients screened, 15 (9.0%) carried the p.Trp378Gly mutation, all in trans with p.Asn370Ser. Three (20%) of the GD patients with the p.Trp378Gly mutation had developed Parkinsonism, and 11 patients had family history of PD. The p.Trp378Gly mutation is the first French-Canadian founder GBA mutation to be described, which leads to synucleinopathies and to GD type 1 when in compound heterozygosity with p.Asn370Ser.<br /> (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adolescent
Adult
Aged
Child, Preschool
Female
Haplotypes
Heterozygote
Humans
Infant
Male
Middle Aged
Polymorphism, Single Nucleotide
Principal Component Analysis
Quebec
Young Adult
Founder Effect
Gaucher Disease genetics
Glucosylceramidase genetics
Glycine genetics
Mutation
Synucleins genetics
Tryptophan genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1399-0004
- Volume :
- 94
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Clinical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 29920646
- Full Text :
- https://doi.org/10.1111/cge.13405