AIMS: Previous reports have indicated that maturity-onset diabetes of the young (MODY) caused by hepatocyte nuclear factor 1A (HNF1A) mutations (MODY3) is the most common MODY subtype in Northern Europe, but population-based prevalence estimates are lacking. We sought to determine the prevalence of HNF1A-MODY in diabetic subjects of a defined Norwegian population (the HUNT2 Study). METHODS: Of the 1972 diabetic HUNT2 subjects, we identified a subgroup of 43 suspected MODY cases based on information on family history, disease onset and anti-glutamic acid decarboxylase autoantibody status. These cases were considered a discovery group for HNF1A mutations and underwent full DNA sequencing. Subsequently, the entire cohort of diabetic HUNT2 subjects was screened for three selected HNF1A mutations. Possible founder effects were examined using the Norwegian MODY Registry. RESULTS: Three subjects from the discovery group harboured HNF1A mutations. Two subjects had the previously described R229Q mutation, one had a novel S6N alteration, whereas the HNF1A hot-spot mutation P291fsinsC was not identified. Genotyping the cohort of diabetic HUNT2 subjects identified five additional R229Q-positive subjects. Microsatellite analysis performed for all R229Q-positive probands of the Norwegian MODY Registry and those found in the HUNT2 population revealed that 17 of 18 (94%) had genotypes consistent with a common haplotype. CONCLUSIONS: Clinical MODY criteria were fulfilled in 2.2% of diabetic HUNT2 subjects. The minimum prevalence of HNF1A-MODY among diabetic HUNT2 subjects was 0.4%. Because of founder effects, registry-based prevalence studies probably need to be very large and they should also include prospectively collected phenotypes and extensive mutation screening to establish the true prevalence of MODY.
AIMS: Previous reports have indicated that maturity-onset diabetes of the young (MODY) caused by hepatocyte nuclear factor 1A (HNF1A) mutations (MODY3) is the most common MODY subtype in Northern Europe, but population-based prevalence estimates are lacking. We sought to determine the prevalence of HNF1A-MODY in diabetic subjects of a defined Norwegian population (the HUNT2 Study). METHODS: Of the 1972 diabetic HUNT2 subjects, we identified a subgroup of 43 suspected MODY cases based on information on family history, disease onset and anti-glutamic acid decarboxylase autoantibody status. These cases were considered a discovery group for HNF1A mutations and underwent full DNA sequencing. Subsequently, the entire cohort of diabetic HUNT2 subjects was screened for three selected HNF1A mutations. Possible founder effects were examined using the Norwegian MODY Registry. RESULTS: Three subjects from the discovery group harboured HNF1A mutations. Two subjects had the previously described R229Q mutation, one had a novel S6N alteration, whereas the HNF1A hot-spot mutation P291fsinsC was not identified. Genotyping the cohort of diabetic HUNT2 subjects identified five additional R229Q-positive subjects. Microsatellite analysis performed for all R229Q-positive probands of the Norwegian MODY Registry and those found in the HUNT2 population revealed that 17 of 18 (94%) had genotypes consistent with a common haplotype. CONCLUSIONS: Clinical MODY criteria were fulfilled in 2.2% of diabetic HUNT2 subjects. The minimum prevalence of HNF1A-MODY among diabetic HUNT2 subjects was 0.4%. Because of founder effects, registry-based prevalence studies probably need to be very large and they should also include prospectively collected phenotypes and extensive mutation screening to establish the true prevalence of MODY.
Authors: Siri Atma W Greeley; Rochelle N Naylor; Lindsay S Cook; Susan E Tucker; Rebecca B Lipton; Louis H Philipson Journal: J Diabetes Sci Technol Date: 2011-07-01
Authors: Siri Atma W Greeley; Susan E Tucker; Rochelle N Naylor; Graeme I Bell; Louis H Philipson Journal: Trends Endocrinol Metab Date: 2010-04-29 Impact factor: 12.015
Authors: H U Irgens; J Molnes; B B Johansson; M Ringdal; T Skrivarhaug; D E Undlien; O Søvik; G Joner; A Molven; P R Njølstad Journal: Diabetologia Date: 2013-04-27 Impact factor: 10.122
Authors: Jason Flannick; Nicola L Beer; Alexander G Bick; Vineeta Agarwala; Janne Molnes; Namrata Gupta; Noël P Burtt; Jose C Florez; James B Meigs; Herman Taylor; Valeriya Lyssenko; Henrik Irgens; Ervin Fox; Frank Burslem; Stefan Johansson; M Julia Brosnan; Jeff K Trimmer; Christopher Newton-Cheh; Tiinamaija Tuomi; Anders Molven; James G Wilson; Christopher J O'Donnell; Sekar Kathiresan; Joel N Hirschhorn; Pål R Njølstad; Tim Rolph; J G Seidman; Stacey Gabriel; David R Cox; Christine E Seidman; Leif Groop; David Altshuler Journal: Nat Genet Date: 2013-10-06 Impact factor: 38.330