BACKGROUND: Maturity-onset diabetes of the young, type 2 (MODY2) is caused by mutations in the glucokinase gene (GCK). The aim of our study was to determine the prevalence of GCK mutations in the Norwegian MODY Registry and to delineate the clinical phenotype of identified GCK mutation carriers. METHODS: We screened 122 probands referred to the MODY Registry for mutations in GCK and studied extended families with MODY2. RESULTS: We found 2 novel (S76Y and N231S) and 13 previously reported (V62A, G72R, L146R, R191W, A208T, M210K, Y215X, M235T, R275C, E339G, R377C, S453L, and IVS5+1G>C) GCK mutations in 23 probands and in their 33 family members. The prevalence of MODY2 was 12% in the Norwegian MODY Registry. The subjects with GCK mutations had features of mild diabetes. Yet, 15 of 56 MODY2 subjects were treated with oral drugs or insulin. Three subjects had retinopathy and one had macrovascular disease. Also, a limited number of cases had elevated fasting serum triglyceride values. Moreover, two GCK mutation carriers were diagnosed with type 1 diabetes. CONCLUSIONS: According to our diagnostic screening of GCK in the MODY Registry, MODY2 is less prevalent than MODY3 in Norway but is likely to be underreported. Recognizing MODY2 in diabetic patients is important in order to prevent overtreatment. Finally, our study demonstrates the co-occurrence of MODY2 in families with type 1 or type 2 diabetes.
BACKGROUND: Maturity-onset diabetes of the young, type 2 (MODY2) is caused by mutations in the glucokinase gene (GCK). The aim of our study was to determine the prevalence of GCK mutations in the Norwegian MODY Registry and to delineate the clinical phenotype of identified GCK mutation carriers. METHODS: We screened 122 probands referred to the MODY Registry for mutations in GCK and studied extended families with MODY2. RESULTS: We found 2 novel (S76Y and N231S) and 13 previously reported (V62A, G72R, L146R, R191W, A208T, M210K, Y215X, M235T, R275C, E339G, R377C, S453L, and IVS5+1G>C) GCK mutations in 23 probands and in their 33 family members. The prevalence of MODY2 was 12% in the Norwegian MODY Registry. The subjects with GCK mutations had features of mild diabetes. Yet, 15 of 56 MODY2 subjects were treated with oral drugs or insulin. Three subjects had retinopathy and one had macrovascular disease. Also, a limited number of cases had elevated fasting serum triglyceride values. Moreover, two GCK mutation carriers were diagnosed with type 1 diabetes. CONCLUSIONS: According to our diagnostic screening of GCK in the MODY Registry, MODY2 is less prevalent than MODY3 in Norway but is likely to be underreported. Recognizing MODY2 in diabeticpatients is important in order to prevent overtreatment. Finally, our study demonstrates the co-occurrence of MODY2 in families with type 1 or type 2 diabetes.
Authors: Bente B Johansson; Henrik U Irgens; Janne Molnes; Paweł Sztromwasser; Ingvild Aukrust; Petur B Juliusson; Oddmund Søvik; Shawn Levy; Torild Skrivarhaug; Geir Joner; Anders Molven; Stefan Johansson; Pål R Njølstad Journal: Diabetologia Date: 2016-12-02 Impact factor: 10.122
Authors: May Sanyoura; Lisa Letourneau; Amy E Knight Johnson; Daniela Del Gaudio; Siri Atma W Greeley; Louis H Philipson; Rochelle N Naylor Journal: Diabetes Res Clin Pract Date: 2019-05-04 Impact factor: 5.602
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
Authors: Anna M Steele; Kirsty J Wensley; Sian Ellard; Rinki Murphy; Maggie Shepherd; Kevin Colclough; Andrew T Hattersley; Beverley M Shields Journal: PLoS One Date: 2013-06-14 Impact factor: 3.240
Authors: J Hulín; M Škopková; T Valkovičová; S Mikulajová; M Rosoľanková; P Papcun; D Gašperíková; J Staník Journal: Physiol Res Date: 2020-11-02 Impact factor: 1.881