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Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients
Author(s) -
Garin Intza,
Rica Itxaso,
Estalella Itziar,
Oyarzabal Mirentxu,
RodríguezRigual Mercedes,
Pedro Jose Ignacio San,
PérezNanclares Gustavo,
FernándezRebollo Eduardo,
Busturia Maria Angeles,
Castaño Luis,
De Nanclares Guiomar Pérez
Publication year - 2008
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03214.x
Subject(s) - haploinsufficiency , glucokinase , multiplex ligation dependent probe amplification , mutation , medicine , maturity onset diabetes of the young , endocrinology , gene mutation , point mutation , biology , gene , genotype , genetics , phenotype , diabetes mellitus , exon
Summary Objective The aim of this study was to characterize glucokinase ( GCK ) alterations in maturity‐onset diabetes of the young 2 (MODY2)‐suspected patients and to investigate their clinical characteristics in relation to the parental origin of the mutation. Patients and methods We studied a group of 57 unrelated Spanish patients presenting with MODY2 phenotype. Patients without mutation in the coding region of the GCK gene were screened for rearrangements by Multiplex Ligation‐dependent Probe Amplification (MLPA). After classification according to the parental origin of the mutation, clinical characteristics were compared between the groups. Results We detected a point mutation or small deletion or insertion of the GCK gene in 47 patients (82·5%); 19 mutations were novel. In addition, we found a whole‐gene deletion by MLPA. Patients carrying a GCK gene defect and those with MODY of unknown genetic origin shows similar phenotypes. Comparison of clinical parameters according to the origin of the mutation did not show any differences in the birth weight (BW) nor in age at diagnosis. Patients who inherited the mutation from the father had higher fasting glucose levels at diagnosis. Conclusion Although the presence of haploinsufficiency of GCK is not a common cause of MODY2, gene dose analysis should be performed when no mutation is found. Strict maternal euglycaemia can contribute to intrauterine growth restriction and low BW when the foetus has inherited the GCK mutation from the mother. As foetal genotype in generally is not known, serial foetal abdominal scans may act as a surrogate for this.