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目的寻找维吾尔族早发糖尿病(MODY)3家系先证者肝细胞核因子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 487Asn);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 exon4V264V和exon7Q497Q为新发现的单核苷酸多态性位点,未检测到HNF1α基因的突变。
Objective To find the mutation sites or polymorphic sites of hepatocyte nuclear factor 1α (HNF1α) gene in proband in 3 families with MODY in Uygur nationality. Methods Genomic DNA of probands was extracted and all the exons, exons and introns of HNF1α gene were sequenced by Sanger sequencing. Results 12 genetic polymorphism sites were screened. The CTC-CTG codon 17 of exon 1 is a leucine synonymous mutation (Leu17Leu) in exon 1. The codon ATC → CTC in codon 27 is leucine instead of isoleucine (Ile27Leu), which is a missense mutation ; Codon 264 of GTC → GTT in exon 4 is a valine synonymous mutation (Val264Val), synonymous mutation (Leu459Leu) of leucine in CTG → TTG is found in codon 459 of exon 7, AGC → AAC at codon 487 is the missense mutation (Ser 487Asn) from serine to asparagine; CAG → CAA at codon 497 is a synonymous mutation of Gln (Gln497Gln). The five intron regions were found to contain mutations IVS1nt-42G> A and IVS1nt-91A> G in intron 1, IVS2nt-23C> T in intron 2, IVS5nt + 9C> G in intron 5, IVS7nt + 7G> A of intron 7 and IVS9nt-24G> T of intron 9. Conclusion Exon4V264V and exon7Q497Q are newly discovered single nucleotide polymorphisms. No mutation of HNF1α gene was detected.