Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 81, Issue 2, Pages 375-382Publisher
UNIV CHICAGO PRESS
DOI: 10.1086/519174
Keywords
-
Categories
Funding
- Wellcome Trust [lshm-ct-2006-518153] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available