title: Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes.
abstract: Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.
authors.affiliation: Department of Endocrinology, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China; Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China; Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China; The Central Laboratory of the Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Tai-Cheng
authors.initials: TC
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Yong-Ying
authors.initials: YY
authors.lastname: Liu
authors.affiliation: The Central Laboratory of the Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Yunnan University, Kunming, Yunnan 650091, China.
authors.forename: Wen-Xue
authors.initials: WX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 2E8.
authors.forename: David M
authors.initials: DM
authors.lastname: Irwin
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006367:HeLa Cells; D056945:Hep G2 Cells; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D040941:Heredity; D006801:Humans; D008297:Male; D009035:Mothers; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D005819:Genetic Markers; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4