Knebel B, Jacob S, Boxberg C V, Müller-Wieland D, Kotzka J
Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
Exp Clin Endocrinol Diabetes. 2004 Jun;112(6):298-301. doi: 10.1055/s-2004-820967.
Maturity-onset diabetes of the young is an autosomal dominant form of non-insulin dependent diabetes mellitus and is caused by mutations in at least six different genes. In the most common forms, i.e. MODY2 and MODY3, the glucokinase (GCK) and the hepatocyte nuclear factor (HNF)-1alpha gene is affected, respectively. We have screened the GCK gene and HNF-1alpha gene by direct sequencing in three German families with early onset type-2-diabetes, possibly MODY. Next to known polymorphisms we have identified two novel intronic insertions in GCK and a novel non-sense mutation in exon 9 (C364 X). The latter mutation has an autosomal dominant inheritance pattern. Accordingly, this novel mutation segregates with diabetes phenotype in this family.
青年发病的成年型糖尿病是一种常染色体显性非胰岛素依赖型糖尿病，由至少六个不同基因的突变引起。在最常见的类型中，即MODY2和MODY3，葡萄糖激酶（GCK）和肝细胞核因子（HNF）-1α基因分别受到影响。我们通过直接测序对三个可能为MODY的早发型2型糖尿病德国家庭的GCK基因和HNF-1α基因进行了筛查。除了已知的多态性外，我们在GCK基因中鉴定出两个新的内含子插入以及外显子9中的一个新的无义突变（C364X）。后一种突变具有常染色体显性遗传模式。因此，这个新突变在该家族中与糖尿病表型共分离。
