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Identification of novel GCK and HNF1A/TCF1 mutations and polymorphisms in German families with maturity‐onset diabetes of the young (MODY)
Author(s) -
Toaima Dalia,
Näke Andrea,
Wendenburg Jutta,
Praedicow Kirsten,
Rohayem Julia,
Engel Kerstin,
Galler Angela,
Gahr Manfred,
LeeKirsch Min Ae
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9334
Subject(s) - hnf1a , maturity onset diabetes of the young , biology , genetics , identification (biology) , maturity (psychological) , german , mutation , gene , medicine , endocrinology , psychology , history , developmental psychology , botany , archaeology
Maturity‐onset diabetes of the young is a genetically heterogenous autosomal dominant form of diabetes mellitus, characterized by an early age at onset and a primary defect in beta‐cell function. Forty families with a clinical presentation suggestive of MODY were screened for the most common MODY subtypes caused by mutations in the genes encoding glucokinase (GCK, MODY2) and hepatocyte nuclear 1‐alpha (HNF1A/TCF1, MODY3). Overall, 14 mutations were found (35%) giving a relative frequency of 22.5% and 12.5% for MODY2 and MODY3, respectively. Five of the nine GCK mutations identified were novel and included two deletions, two nonsense, and one splice site mutation. The GCK splice donor mutation was shown to result in an aberrant transcript owing to the recruitment of a cryptic splice site. The translated protein is predicted to contain an in frame insertion of nine amino acids. Among the five HNF1A mutations identified, three were novel comprising one missense mutation, one deletion, and one insertion. In addition, several novel polymorphisms within GCK were identified and their allele frequencies estimated. Knowledge of the genetic cause of MODY has significant impact on therapeutic decision making and may help to identify family members at risk for diabetes. © 2005 Wiley‐Liss, Inc.