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Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity‐onset diabetes of the young (MODY)
Author(s) -
Guazzini Barbara,
Gaffi Davide,
Mainieri Davide,
Multari Giuseppe,
Cordera Renzo,
Bertolini Stefano,
Pozza Guido,
Meschi Franco,
Barbetti Fabrizio
Publication year - 1998
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/(sici)1098-1004(1998)12:2<136::aid-humu13>3.0.co;2-v
Subject(s) - maturity onset diabetes of the young , glucokinase , missense mutation , biology , proband , genetics , endocrinology , diabetes mellitus , medicine , mutation , gene , allele , mutant
The maturity‐onset diabetes of the young (MODY), an autosomal dominant form of non‐insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY1) genes. We have screened the glucokinase gene by the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) in fifteen subjects with clinical characteristics of MODY and one parent with NIDDM, impaired glucose tolerance or gestational diabetes. PCR products with abnormal mobility in DGGE were directly sequenced. We have identified four mutant alleles, three of them (G80S, E221K, G227C) are new missense mutations located in or near the region of the active site cleft of the enzyme. The mutations co‐segregate with hyperglycemia in the families of the three probands, whose biochemical and clinical phenotype is similar to other individuals with MODY 2 mutations. Hum Mutat 12:136, 1998. © 1998 Wiley‐Liss, Inc.