Cao Henian, Shorey Sanam, Robinson John, Metzger Daniel L, Stewart Laura, Cummings Elizabeth, Hegele Robert A
Robarts Research Institute, London, Ontario, Canada.
Hum Mutat. 2002 Dec;20(6):478-9. doi: 10.1002/humu.9090.
Maturity onset diabetes of the young (MODY) is a genetically heterogeneous form of type 2 diabetes that is characterized by autosomal dominant inheritance, onset in early adulthood and a primary defect in insulin secretion. Mutations in at least six genes have been shown to underlie MODY, including mutations in GCK (encoding glucokinase, also called MODY2) and mutations in HNF1A (encoding hepatocyte nuclear factor-1alpha, also called MODY3). We sequenced genomic DNA from probands of seven Canadian MODY families. In four probands, we detected four novel GCK mutations, namely IVS2-7G>A, G72R, T206R and S263P. In three other probands, we detected three HNF1A mutations, of which two were novel, namely 1051delCA and Q250X, and one had been previously reported, namely R131Q. The novel mutations expand the spectrum of MODY mutations. In addition, knowledge of the specific defect can be used to pre-symptomatically identify family members at risk for developing MODY.
青年发病的成年型糖尿病（MODY）是2型糖尿病的一种遗传异质性形式，其特征为常染色体显性遗传、成年早期发病以及胰岛素分泌的原发性缺陷。已证实至少六个基因的突变是MODY的发病基础，包括GCK（编码葡萄糖激酶，也称为MODY2）的突变和HNF1A（编码肝细胞核因子-1α，也称为MODY3）的突变。我们对来自七个加拿大MODY家系的先证者的基因组DNA进行了测序。在四个先证者中，我们检测到四个新的GCK突变，即IVS2-7G>A、G72R、T206R和S263P。在另外三个先证者中，我们检测到三个HNF1A突变，其中两个是新的，即1051delCA和Q250X，另一个之前已被报道，即R131Q。这些新突变扩展了MODY突变的谱。此外，对特定缺陷的了解可用于在出现症状前识别有患MODY风险的家庭成员。
