title: Prevalence and clinical phenotype of the p.Val226Met glucokinase gene mutation in French Canadians in Quebec, Canada.
abstract: Our objectives were to describe the clinical phenotype of maturity-onset diabetes of the young (MODY) type 2 in a group of French Canadians and estimate its prevalence in this population. Index cases were identified by an abnormal fasting blood glucose (FBG) upon metabolic evaluation for dyslipidemia. Mutational analyses confirmed that all probands and affected family members were positive for the same glucokinase mutation, p.Val226Met. The prevalence of this mutation was estimated from a representative sample of French Canadians. Eleven individuals in 5 different families were diagnosed with MODY 2. Four of the five families originated from the same region in Quebec. In affected children (n = 6), the median age at diagnosis was 7.6 years (range = 2.9-9.4). All were asymptomatic. The range of FBG was 4.4-7.0 mmol/L; 5 out of the 6 pediatric patients had normal FBG values during the course of follow-up. One child presented with consistently normal FBG. Four of the adults who screened positive for MODY 2 had been previously misdiagnosed with type 2 DM, and one female had a history of gestational DM. The estimated prevalence of heterozygotes for the p.Val226Met mutation in French Canadians was 0.057% (95%CI 0.01-0.32%). In conclusion, this report presents the first confirmed case of MODY 2 with persistently normal FBG. In children and adolescents, a normal FBG does not allow for the exclusion of a MODY 2 diagnosis. Our results are consistent with a founder effect for the p.Val226Met glucokinase gene mutation in Quebec, Canada.
authors.affiliation: Department of Pediatrics, Ste-Justine Hospital and Université de Montréal, Montreal, QC, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Henderson
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.forename: Edgard
authors.initials: E
authors.lastname: Delvin
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
authors.forename: Marie
authors.initials: M
authors.lastname: Lambert
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005602:France / Q000208:ethnology; D005941:Glucokinase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D015995:Prevalence; D011792:Quebec / Q000453:epidemiology; D014633:Valine / Q000235:genetics
chemical_list: D008715:Methionine; D005941:Glucokinase; D014633:Valine