This Article Full Text Full Text (PDF) All Versions of this Article: 90/8/4607    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Johansen, A. Articles by Hansen, T. Search for Related Content PubMed PubMed Citation Articles by Johansen, A. Articles by Hansen, T. Related Collections Pediatric Endocrinology Diabetes and Insulin

Half of Clinically Defined Maturity-Onset Diabetes of the Young Patients in Denmark Do Not Have Mutations in HNF4A, GCK, and TCF1

Steno Diabetes Center and Hagedorn Research Institute (A.J., J.E., O.P., T.H), DK-2820 Gentofte, Denmark; Glostrup University Hospital (H.B.M.), DK-2600 Glostrup, Denmark; Faculty of Health Science (H.B.M.), University of Copenhagen, DK-2200 Copenhagen, Denmark; and Faculty of Health Science (O.P.), University of Aarhus, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Anders Johansen, M.D., Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. E-mail: adjo{at}steno.dk.

Aims/Hypothesis: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of diabetes characterized by an autosomal dominant inheritance, an early clinical onset, and a primary defect in ß-cell function. The aims of the present study were to examine the prevalence and nature of mutations in the three common MODY genes, HNF4A, GCK, and TCF1, in Danish patients with a clinical diagnosis of MODY and to describe metabolic differences in probands with and without mutations in HNF4A, GCK, and TCF1.

Methods: Seventy-eight unrelated subjects of Danish Caucasian origin (29 men, 49 women) and their 351 family members were examined. The promotor and coding regions including intron-exon boundaries of HNF4A, GCK, and TCF1 were examined by denaturing HPLC and/or direct sequencing.

Results: We identified 29 different mutations in 38 MODY families. Fifteen of the mutations were novel. The variants segregated with diabetes within the families, and none of the variants were found in 100 normal Danish chromosomes. Our findings suggest a relative prevalence of 3% of MODY1 (two different mutations in two families), 10% of MODY2 (seven in eight), and 36% of MODY3 (21 in 28) among Danish kindred clinically diagnosed as MODY. No significant differences in biochemical and anthropometric measurements were observed at baseline examinations.

Conclusions: Forty-nine percent of the families carried mutations in the three examined MODY genes. Our findings highlight that unidentified MODY genes may play a central role for diabetes characterized by autosomal dominant transmission. Furthermore, baseline measurements of various anthropometric and biochemical variables are not appropriate markers of MODYX.