【摘要】  目的  寻找维吾尔族早发糖尿病（MODY）3家系先证者1α（HNF1α）基因的突变位点或多态性位点。 方法  抽提先证者基因组DNA，PCR扩增，Sanger测序肝细胞核因子1α（HNF1α）基因所有外显子和外显子与内含子拼接区。结果  筛查到12种基因多态性位点。其中，外显子1的17号密码子CTC-CTG为亮氨酸的同义突变（Leu17Leu），27号密码子ATC→CTC是亮氨酸替代异亮氨酸（Ile27Leu），为错义突变；外显子4的264号密码子GTC→GTT是缬氨酸的同义突变（Val264Val），在外显子7区459号密码子发现CTG→TTG为亮氨酸的同义突变（Leu459Leu），487号密码子AGC→AAC是丝氨酸变为天冬酰胺的错义突变（Ser 487 Asn）；497号密码子发生了CAG→CAA，是谷氨酰胺的同义突变（Gln497Gln）。发现5个内含子区域的变异，即内含子1的IVS1nt-42G＞A和IVS1nt-91A＞G，内含子2的IVS2nt-23C＞T，内含子5的IVS5nt+9C＞G，内含子7的IVS7nt+7G＞A，内含子9的IVS9nt-24G＞T。  结论  exon4 V264V和exon7 Q497Q 为新发现的单核苷酸多态性位点，未检测到HNF1α基因的突变。

 MODY3 gene analysis in an Uyghur patient with early onset diabetes

【Abstract】  Objective To investigate mutations in hepatocyte nuclear factor 1α（HNF-1α,MODY3） gene in an Uyghur patient with clinically diagnosis of maturity-onset diabetes of the young (MODY). Methods  DNA of the patient was extracted. All exons ( exon 1 to 10) and flanking intron regions of the HNF1α gene were amplified by PCR and sequenced by Sanger methods. Results  12 variants in HNF-1α genes were identified. They are exon1 p.Leu17Leu (synonymous mutation), exon1 p.Ile27Leu(nonsynonymous mutation), Exon4 p. Val264Val(synonymous mutation), Exon7 p.Leu459Leu(synonymous mutation), Exon7 p.Ser487Asn(nonsynonymous mutation) , Exon7 p.Gln497Gln (synonymous mutation), intron1 IVS1nt-42 G>A, Intron1 IVS1nt-91 A>G, Intron2 IVS2nt-23 C>T, Intron5 IVS5nt+9 C>G, Intron7 IVS7nt+7 G>A, and Intron9 IVS9nt-24 G>T. Conclusion  Exon4 V264V and exon7 Q497Q were two newly discovered variants in HNF-1αgene. No pathogenic mutations were found in HNF-1α.