Author/Authors :
ZHOU, Peng Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China , WEI, Ran Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China , GUO, Zhenkui Shandong Institute of Endocrine and Metabolic Disease, Jinan, Shandong, China , ZHU, Haining Zibo Center for Disease Control and Prevention, Zibo, Shandong, China , CAMPBELL, Desmond Dept. of Psychiatry - University of Hong Kong - Pokfulam - Hong Kong Special Administrative Region (H.K.S.A.R.), China , LI, Qi Dept. of Psychiatry - University of Hong Kong - Pokfulam - Hong Kong Special Administrative Region (H.K.S.A.R.), China , XU, Xiaoqun Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China , WANG, Junfu Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China , LUAN, Meng Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China , CHEN, Xing Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China , CHEN, Gang Key Laboratory for Tumor Immunity and Genetic Engineering of Shandong Province - Institute of Basic Medicine - Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China
Abstract :
Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders cha-racterized 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 of DNA of each individual within the each group. To-tally 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) be-tween 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.
