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采集该家系15个成员和16例健康对照组的外周血样,提取基因组DNA,应用PCR技术对HNF1ɑ基因全部外显子及外显子内含子拼接区进行扩增,PCR产物直接测序,对发现的碱基改变进行分析。结果本研究中发现3个编码区错义突变:I27L、R272S、S487N,2个同义突变:I17L、L459L,6个非编码区碱基改变:IVS1+91A>G、IVS5+9C>G、IVS7+7G>A、IVS8-24T>C、IVS9+197G>T、IVS9+438G>A。其中R272S、IVS5+9C>G、IVS8-24T>C、IVS9+197G>T、IVS9+438G>A只出现于该家系中;除R272S外的其他碱基改变均可在NCBI中查到相关SNP信息,为多态性改变,且和糖尿病的发生无相关性,而错义突变R272S与糖尿病共分离。结论该家系可能为HNF1ɑ基因R272S突变所致的MODY3家系。
Peripheral blood samples of 15 members of the pedigree and 16 healthy controls were collected and genomic DNA was extracted. PCR was used to amplify the splicing region of all exons and exons of HNF1ɑ gene, and the PCR products were directly sequenced. Base changes were analyzed. Results There were three missense mutations in coding region: I27L, R272S and S487N, two synonymous mutations: I17L and L459L, and the changes in six non-coding regions were IVS1 + 91A> G and IVS5 + 9C> IVS7 + 7G> A, IVS8-24T> C, IVS9 + 197G> T, IVS9 + 438G> A. Among them, R272S, IVS5 + 9C> G, IVS8-24T> C, IVS9 + 197G> T and IVS9 + 438G> A appeared only in this pedigree; other SNPs except R272S could be detected in NCBI The information is polymorphic and has no correlation with the occurrence of diabetes while the missense mutation R272S is co-segregated with diabetes. Conclusion The pedigree may be the MODY3 pedigree caused by the R272S mutation of HNF1ɑ gene.