Three new mutations in the hepatocyte nuclear factor-1α gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization
Three new mutations in the hepatocyte nuclear factor-1α gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization
复制标题
日本糖尿病患者肝细胞核因子1α基因的三种新突变：临床特征和功能特征
作者：
I. Yoshiuchi;K. Yamagata;Qin Yang;H. Iwahashi;K. Okita;K. Yamamoto;T. Oue;A. Imagawa;T. Hamaguchi;Tomoyuki Yamasaki;Y. Horikawa;T. Satoh;Hiromu Nakajima;Jun;Shigeki Higashiyama;Jun;M. Namba;T. Hanafusa;Y. Matsuzawa
Aims/hypothesis. Mutations in the hepatocyte nuclear factor-1α gene are a common cause of the type 3 form of maturity-onset diabetes of the young. We examined the clinical features and molecular basis of hepatocyte nuclear factor-1α (HNF-1α) diabetes. Methods. Thirty-seven Japanese subjects with early onset Type II (non-insulin-dependent) diabetes mellitus and 45 with Type I (insulin-dependent) diabetes mellitus were screened for mutations in this gene. Functional properties of mutant HNF-1α were also investigated. Results. Three new mutations [G415R, R272C and A site of the promoter ( + 102G-to-C)] were found. Insulin secretion was impaired in the three subjects. Insulin and glucagon secretory responses to arginine in the subject with the R272C mutation were also diminished. Molecular biological studies indicated that the G415R mutation generated a protein with about 50 % of the activity of wild-type HNF-1α. The R272C mutation had no transactivating or DNA binding activity and acted in a dominant negative manner. The + 102 G-to-C mutation in the A site of the promoter activity was associated with an increase in promoter activity and it had 42–75 % more activity than the wild-type sequence. Conclusion/interpretation. Mutations in the HNF-1α gene may affect the normal islet function by different molecular mechanisms. [Diabetologia (1999) 42: 621–626]
影响因子：
15.9
作者：
WARD, WK;BOLGIANO, DC;PORTE, D
通讯作者：
PORTE, D
典型家族性 2 型糖尿病中 MODY3/肝细胞核因子 1 α 基因的连锁和分子扫描分析：外显子 8 和 10 中新突变的证据。
DOI：
10.1210/jcem.83.6.4874
发表时间：
1998
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Elbein,SC;Teng,K;Yount,P;Scroggin,E
通讯作者：
Scroggin,E
葡萄糖反调节系统与胰岛素依赖型糖尿病患者的相关性。
影响因子：
20.3
作者：
Cryer,PE;White,NH;Santiago,JV
通讯作者：
Santiago,JV