The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.
Clin Genet
; 94(3-4): 339-345, 2018 10.
Article
in En
| MEDLINE
| ID: mdl-29920646
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tryptophan
/
Founder Effect
/
Synucleins
/
Gaucher Disease
/
Glucosylceramidase
/
Glycine
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Middle aged
Country/Region as subject:
America do norte
Language:
En
Journal:
Clin Genet
Year:
2018
Document type:
Article