Glucksmann M A, Lehto M, Tayber O, Scotti S, Berkemeier L, Pulido J C, Wu Y, Nir W J, Fang L, Markel P, Munnelly K D, Goranson J, Orho M, Young B M, Whitacre J L, McMenimen C, Wantman M, Tuomi T, Warram J, Forsblom C M, Carlsson M, Rosenzweig J, Kennedy G, Duyk G M, Thomas J D
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
Diabetes. 1997 Jun;46(6):1081-6. doi: 10.2337/diab.46.6.1081.
Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) located on chromosome 12q. We have identified four novel HNF-1alpha missense mutations in MODY3 families. In four additional and unrelated families, we observed an identical insertion mutation that had occurred in a polycytidine tract in exon 4. Among those families, one exhibited a de novo mutation at this location. We propose that instability of this sequence represents a general mutational mechanism in MODY3. We observed no HNF-1alpha mutations among 86 unrelated late-onset diabetic patients with relative insulin deficiency. Hence mutations in this gene appear to be most strongly associated with early-onset diabetes.
青年发病的成年型糖尿病3型（MODY3）是一种非胰岛素依赖型糖尿病，由位于12号染色体q臂上的转录因子肝细胞核因子-1α（HNF-1α）突变引起。我们在MODY3家系中鉴定出了4种新的HNF-1α错义突变。在另外4个无亲缘关系的家系中，我们观察到外显子4中一个多聚胞嘧啶区域发生了相同的插入突变。在这些家系中，有一个家系在此位置出现了新发突变。我们认为该序列的不稳定性是MODY3的一种常见突变机制。在86例无亲缘关系的相对胰岛素缺乏的晚发性糖尿病患者中，我们未观察到HNF-1α突变。因此，该基因的突变似乎与早发性糖尿病关联最为密切。
