期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 81, 期 2, 页码 375-382出版社
UNIV CHICAGO PRESS
DOI: 10.1086/519174
关键词
-
资金
- Wellcome Trust [lshm-ct-2006-518153] Funding Source: Medline
Heterozygous activating mutations in the KCNj11 gene encoding the pore-forming Kir6.2 subunit of the pancreatic beta cell KAT, channel are the most common cause of permanent neonatal diabetes (PNDM). Patients with PNDM due to a heterozygous activating mutation in the ABCC8 gene encoding the SUR1 regulatory subunit of the K-ATP, channel have recently been reported. We studied a cohort of 59 patients with permanent diabetes who received a diagnosis before 6 mo of a-e and who did not have a KCNJ11 mutation. ABCC8 gene mutations were identified in 16 of 59 patients and included 8 patients with heterozygous de novo mutations. A recessive mode of inheritance was observed in eight patients with homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据