Genetic research of the gene HNF1A responsible for diabetes mellitus type MODY3 in the Greek population

Doctoral Dissertation uoadl:1305890 470 Read counter

Τομέας Υγείας - Μητέρας - Παιδιού
Library of the School of Health Sciences
Deposit date:
Τάτση Χριστίνα
Dissertation committee:
Χριστίνα Κανακά-Gantenbein
Original Title:
Γενετική διερεύνηση του γονιδίου ΗΝF1Α υπεύθυνου για τον σακχαρώδη διαβήτη τύπου ΜΟDΥ3 στον Ελληνικό πληθυσμό
Translated title:
Genetic research of the gene HNF1A responsible for diabetes mellitus type MODY3 in the Greek population
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-ve 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 amplied
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 amplication (MLPA) for the presence of HNF1A gene
Results: In 16 unrelated patients and 13 of their relatives, 15 mutations were
identied 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 fullling strict clinical criteria for
MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene
are responsible for a signicant proportion of monogenic diabetes in the Greek
population. No clear phenotype–genotype correlations were identied.
MODY diabetes, Μonogenic diabetes, MODY3, HNF1A gene
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