Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients

LOPEZ AP; FOSCALDI SA; PEREZ MS; KROCHIK G; RODRIGUEZ M; TRAVERSA M; PUCHULU FM; HIRSCHLER V; BERGADA I; FRECHTEL GD

EXPERIMENTAL CLINICAL ENDOCRINOLOGY & DIABETES

Año: 2008

0947-7349

Introduction: Mutations in the glucokinase gene (GCK) produce a subtype of Maturity onset diabetes in the young (MODY), named MODY   2. To date over than 190 diff erent mutations have been identifi ed, distributed over the coding regions and the exon – intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the GCK gene, in a MODY clinically characterized Argentinean population. Material and Methods: Seventy unrelated individuals were selected based on MODY clinical features. The study methodology consisted in PCR amplifi cation of the coding regions of the GCK gene, SSCP electrophoresis analysis of the amplifi ed fragments and direct sequencing of the fragments with abnormal electrophoresis pattern. Results: We identified a total of six patients with mutations in the GCK gene. This included two novel mutations: g.1831C > A, g.3792T > A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of MODY 2 among the patients in study reaching to 8.6 % . Discussion: The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of MODY 2 in the population under study. These findings contribute to confi rm the allelic heterogeneity of GCK gene mutations and may provide an insight into the structure-function relationship of GCK.