Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 45 2 2016 02 28 170 178 Peng ZHOU Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China Ran WEI Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China Zhenkui GUO Shandong Institute of Endocrine and Metabolic Disease, Jinan, Shandong, China Haining ZHU Zibo Center for Disease Control and Prevention, Zibo, Shandong, China Desmond CAMPBELL Dept. of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (H.K.S.A.R.), China Qi LI Dept. of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (H.K.S.A.R.), China Xiaoqun XU Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China Junfu WANG Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China Meng LUAN Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China Xing CHEN Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China Gang CHEN Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China 2016 02 28 2016 02 28 Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported. Methods: To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations.DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity ofDNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants. Results: Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001) between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1β (HNF-1β) on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV) of C77T in the non-coding area of exon 1 of HNF-1β was found to be related to MODY5. Conclusion: This novel SNV of HNF-1β contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY.   https://ijph.tums.ac.ir/index.php/ijph/article/view/6101 https://ijph.tums.ac.ir/index.php/ijph/article/download/6101/5300