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
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...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/3582616 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832565598483120128 |
|---|---|
| author | Ying Yang Tai-Cheng Zhou Yong-Ying Liu Xiao Li Wen-Xue Wang David M. Irwin Ya-Ping Zhang |
| author_facet | Ying Yang Tai-Cheng Zhou Yong-Ying Liu Xiao Li Wen-Xue Wang David M. Irwin Ya-Ping Zhang |
| author_sort | Ying Yang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9b91f9c180b74024ada6a542fbaeeaed |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-9b91f9c180b74024ada6a542fbaeeaed2025-02-03T01:07:16ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/35826163582616Identification 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 DiabetesYing Yang0Tai-Cheng Zhou1Yong-Ying Liu2Xiao Li3Wen-Xue Wang4David M. Irwin5Ya-Ping Zhang6Department of Endocrinology, The Second People’s Hospital of Yunnan Province, Kunming, Yunnan 650021, ChinaDepartment of Endocrinology, The Second People’s Hospital of Yunnan Province, Kunming, Yunnan 650021, ChinaDepartment of Endocrinology, The Second People’s Hospital of Yunnan Province, Kunming, Yunnan 650021, ChinaThe Central Laboratory of the Second People’s Hospital of Yunnan Province, Kunming, Yunnan 650021, ChinaLaboratory of Biochemistry and Molecular Biology, Yunnan University, Kunming, Yunnan 650091, ChinaState Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, ChinaLaboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, ChinaMaturity-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.http://dx.doi.org/10.1155/2016/3582616 |
| spellingShingle | Ying Yang Tai-Cheng Zhou Yong-Ying Liu Xiao Li Wen-Xue Wang David M. Irwin Ya-Ping Zhang 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 Journal of Diabetes Research |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://dx.doi.org/10.1155/2016/3582616 |
| work_keys_str_mv | AT yingyang identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes AT taichengzhou identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes AT yongyingliu identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes AT xiaoli identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes AT wenxuewang identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes AT davidmirwin identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes AT yapingzhang identificationofhnf4amutationpt130iandhnf1amutationspi27landps487ninahanchinesefamilywithearlyonsetmaternallyinheritedtype2diabetes |