Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry

Authors

  • Jørn V Sagen,

    1. Section for Endocrinology, Institute of Medicine, University of Bergen, Bergen, Norway
    2. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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  • Lise Bjørkhaug,

    1. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    2. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
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  • Janne Molnes,

    1. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    2. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
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  • Helge Ræder,

    1. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    2. Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
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  • Louise Grevle,

    1. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    2. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
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  • Oddmund Søvik,

    1. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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  • Anders Molven,

    1. Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway
    2. Department of Pathology, Haukeland University Hospital, Bergen, Norway
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  • Pål R Njølstad

    Corresponding author
    1. Section for Pediatrics, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    2. Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
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Pål R Njølstad, MD, PhD
Section for Pediatrics
Department of Clinical Medicine
University of Bergen
N-5021 Bergen
Norway.
Tel: +47 55975153;
fax: +47 55975147;
e-mail: pal.njolstad@uib.no

Abstract

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.

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