Study Of Genetic Variability Of Hepatocyte Nuclear Factor-1α Gene In Three Chinese Pedigrees With Early-onset Diabetes

Objective:To explore whether HNF1αgene mutations are the main pathogenic factors which could cause the diseases in three Chinese family that suspected MODY pedigrees.Method:Collect peripheral blood sample of this three familiese and 16 cases of healthy controls and then extract genomic DNA.Al1 the exons and exon/intron splice sites of MODY3 gene were amplified by PCR,and PCR products were sequenced to identify the DNA variants.The identified sequence changes were genotyped.Results:We identified 3 misense mutations in coding region including R272S、I27L、S487N;2 silent mutations in coding region including I17L、L459L,and 6 DNA variants in noncoding region including IVS1+91A>G、IVS5+9C>G、IVS7+7G>A、IVS8-24T>C、IVS9+197G>T、IVS9+438G>A.R272S、IVS5+9C>G、IVS8-24T>C、IVS9+197G>T、IVS9+438G>A were found only in first family.The sequence changes we found are all SNPs except R272 S and have no correlation with diabetes.The mutation R272 S was co-segregated with diabetes.Conclusion:The F1 family may be a MODY3 predigree that caused by HNF1 a genetic mutation R272 S.