Whole-exome sequencing identifies a novel INS mutation causative of maturity-onset diabetes of the young 10
文献类型：期刊论文
| 作者 | Yan, Jing2; Jiang, Feng2; Zhang, Rong2; Zhou, Zhou2; Ren, Wei2; Peng, Danfeng2; Hu, Cheng2; Jia, Weiping2; Xu, Tongfu3; Liu, Yong3 |
| 刊名 | JOURNAL OF MOLECULAR CELL BIOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 9期号:5页码:376-383 |
| 关键词 | whole-exome sequencing causative mutation MODY10 endoplasmic reticulum stress |
| ISSN号 | 1674-2788 |
| DOI | 10.1093/jmcb/mjx039 |
| 文献子类 | Article |
| 英文摘要 | Monogenic diabetes is often misdiagnosed with type 2 diabetes due to overlapping characteristics. This study aimed to discover novel causative mutations of monogenic diabetes in patients with clinically diagnosed type 2 diabetes and to explore potential molecular mechanisms. Whole-exome sequencing was performed on 31 individuals clinically diagnosed with type 2 diabetes. One novel heterozygous mutation (p.Ala2Thr) in INS was identified. It was further genotyped in an additional case-control population (6523 cases and 4635 controls), and this variant was observed in 0.09% of cases. Intracellular trafficking of insulin proteins was assessed in INS1-E and HEK293T cells. p.Ala2Thr preproinsulin-GFP was markedly retained in the endoplasmic reticulum (ER) in INS1-E cells. Activation of the PERK-eIF2 alpha-ATF4, IRE1 alpha-XBP1, and ATF6 pathways as well as upregulated ER chaperones were detected in INS1-E cells transfected with the p.Ala2Thr mutant. In conclusion, we identified a causative mutation in INS responsible for maturity-onset diabetes of the young 10 (MODY10) in a Chinese population and demonstrated that this mutation affected beta cell function by inducing ER stress. |
| 学科主题 | Cell Biology |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; INSULIN GENE-MUTATIONS ; CHINESE ; POPULATION ; MELLITUS ; RISK ; PREVALENCE |
| 语种 | 英语 |
| WOS记录号 | WOS:000417761200004 |
| 出版者 | OXFORD UNIV PRESS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1138]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Southern Med Univ, Fengxian Cent Hosp, Inst Metab Dis, Shanghai, Peoples R China, 2.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Shanghai Key Lab Diabet Mellitus,Shanghai Key Cli, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Chinese Acad Sci, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yan, Jing,Jiang, Feng,Zhang, Rong,et al. Whole-exome sequencing identifies a novel INS mutation causative of maturity-onset diabetes of the young 10[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2017,9(5):376-383. |
| APA | Yan, Jing.,Jiang, Feng.,Zhang, Rong.,Zhou, Zhou.,Ren, Wei.,...&,.(2017).Whole-exome sequencing identifies a novel INS mutation causative of maturity-onset diabetes of the young 10.JOURNAL OF MOLECULAR CELL BIOLOGY,9(5),376-383. |
| MLA | Yan, Jing,et al."Whole-exome sequencing identifies a novel INS mutation causative of maturity-onset diabetes of the young 10".JOURNAL OF MOLECULAR CELL BIOLOGY 9.5(2017):376-383. |
入库方式： OAI收割
来源：上海营养与健康研究所
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