Gragnoli C, Lindner T, Cockburn B N, Kaisaki P J, Gragnoli F, Marozzi G, Bell G I
Howard Hughes Medical Institute, University of Chicago, Illinois, USA.
Diabetes. 1997 Oct;46(10):1648-51. doi: 10.2337/diacare.46.10.1648.
Recent studies have shown that mutations in the transcription factor hepatocyte nuclear factor (HNF)-1 alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). These studies have identified mutations in the mRNA and protein coding regions of this gene that result in the synthesis of an abnormal mRNA or protein. Here, we report an Italian family in which an A-->C substitution at nucleotide-58 of the promoter region of the HNF-1 alpha gene cosegregates with MODY. This mutation is located in a highly conserved region of the promoter and disrupts the binding site for the transcription factor HNF-4 alpha, mutations in the gene encoding HNF-4 alpha being another cause of MODY (MODY1). This result demonstrates that decreased levels of HNF-1 alpha per se can cause MODY. Moreover, it indicates that both the promoter and coding regions of the HNF-1 alpha gene should be screened for mutations in subjects thought to have MODY because of mutations in this gene.
近期研究表明，转录因子肝细胞核因子（HNF）-1α的突变是青年发病型成年糖尿病（MODY3）的一种病因。这些研究已在该基因的mRNA和蛋白质编码区域鉴定出突变，这些突变导致异常mRNA或蛋白质的合成。在此，我们报告一个意大利家族，其中HNF-1α基因启动子区域核苷酸-58处的A→C替换与MODY共分离。此突变位于启动子的一个高度保守区域，破坏了转录因子HNF-4α的结合位点，编码HNF-4α的基因中的突变是MODY（MODY1）的另一个病因。这一结果表明，HNF-1α本身水平降低可导致MODY。此外，这表明对于因该基因发生突变而被认为患有MODY的受试者，应筛查HNF-1α基因的启动子和编码区域中的突变。
