The spectrum of HNF1A gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations

Authors

  • Christina Tatsi,

    1. Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University School of Medicine, ‘Agia Sophia’ Children's Hospital, Athens, Greece
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  • Christina Kanaka-Gantenbein,

    1. Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University School of Medicine, ‘Agia Sophia’ Children's Hospital, Athens, Greece
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  • Adriani Vazeou-Gerassimidi,

    1. Diabetes Center, P. & A. Kyriakou Children's Hospital, Athens, Greece
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  • Dionysios Chrysis,

    1. Department of Pediatrics, Division of Endocrinology, University of Patras School of Medicine, Rio, Greece
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  • Dimitrios Delis,

    1. Diabetes Center, P. & A. Kyriakou Children's Hospital, Athens, Greece
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  • Nikolaos Tentolouris,

    1. First Department of Propaedeutic and Internal Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece
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  • Catherine Dacou-Voutetakis,

    1. Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University School of Medicine, ‘Agia Sophia’ Children's Hospital, Athens, Greece
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  • George P Chrousos,

    1. Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University School of Medicine, ‘Agia Sophia’ Children's Hospital, Athens, Greece
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  • Amalia Sertedaki

    Corresponding author
    1. Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University School of Medicine, ‘Agia Sophia’ Children's Hospital, Athens, Greece
    • Corresponding author: Amalia Sertedaki, PhD,

      Division of Endocrinology, Diabetes and Metabolism,

      First Department of Pediatrics,

      University of Athens School of Medicine,

      ‘Agia Sophia’ Children's Hospital,

      Thivon & Livadias Street,

      11527-Athens,

      Greece.

      Tel: +30 210 7467475, +306932-416686;

      fax: +30 211 7700062;

      e-mail: aserted@med.uoa.gr

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Abstract

Objective

Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1–2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients.

Design and methods

Three hundred ninety-five patients were referred to our center because of suspected MODY during a period of 15 yr. The use of Denaturing Gradient Gel Electrophoresis of polymerase chain reaction amplified DNA revealed 72 patients carrying Glucokinase gene mutations (MODY2) and 8 patients carrying HNF1A gene mutations (MODY3). After using strict criteria, 54 patients were selected to be further evaluated by direct sequencing or by multiplex ligation probe amplification (MLPA) for the presence of HNF1A gene mutations.

Results

In 16 unrelated patients and 13 of their relatives, 15 mutations were identified in the HNF1A gene. Eight of these mutations were previously reported, whereas seven were novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location.

Conclusions

In our cohort of patients fulfilling strict clinical criteria for MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene are responsible for a significant proportion of monogenic diabetes in the Greek population. No clear phenotype–genotype correlations were identified.

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