No abstract

Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials.

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.

No abstract

Background: In resource-limited settings, screening for gestational diabetes (GDM) is not routine. Standard commercial glucose preparations are often not available. Objectives: To test a locally accessible, cheaper alternative glucose source (AGS) for GDM screening in Haiti. Methods: Double cross-over trial of 138 pregnant women 24-28 weeks gestational age. Two one-step 75g oral glucose tolerance tests (oGTT) with capillary blood glucose (CBG) obtained at 0, 1 and 2h were performed 3-5 days apart with the standard glucose drink Glucola and with AGS. Each participant served as her own control. Logistic and linear regression were used to assess AGS-CBG as a predictor of GDM and of Glucola-CBG, respectively. Tolerance of AGS was surveyed. Results: Fourteen women (10%) had GDM, and 5, 2, and 7 were diagnosed based on Glucola-CBG of >92, >180, and >163 mg/dl at 0, 1 and 2h, respectively. At 1 and 2h, mean AGS-CBG vs. Glucola-CBG was 107 vs. 126 (p<.0001) and 89 vs. 113 mg/dl (p<.0001), respectively, and they were positively correlated (r=0.65 and r=0.68, p≤0001). The 1h AGS-CBG had an area under the curve of 0.82 (p=0.0002) to predict GDM. A cut-off of ≥120 mg/dl had a sensitivity, specificity, positive and negative predictive value of 100%, 78%, 25% and 100% to predict GDM not diagnosed by a fasting CBG. Conclusion: Using a fasting CBG of >92 mg/dL and a 1h post-AGS CBG of ≥120 mg/dL, AGS can determine the need for a Glucola-based oGTT, avoiding 3 out of 4 Glucola based tests. Women prefer AGS over Glucola. Disclosure L. Ronciere: None. B. Coriolan: None. R. Destine: None. C. Belanger-Bishinga: None. I. Malhame: None. J.E. von Oettingen: None. Funding McGill University