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.
Subject(s)
Founder Effect , Gaucher Disease/genetics , Glucosylceramidase/genetics , Glycine/genetics , Mutation , Synucleins/genetics , Tryptophan/genetics , Adolescent , Adult , Aged , Child, Preschool , Female , Haplotypes , Heterozygote , Humans , Infant , Male , Middle Aged , Polymorphism, Single Nucleotide , Principal Component Analysis , Quebec , Young AdultABSTRACT
While the impact of seatbelts on injury is favorable, their use is also associated with unique and previously unrecognized patterns of injury. Two cases of combined subclavian and vertebral artery injury, when lap shoulder harness restraints were used, are presented.
