caa a22 4500 397574576 CHVBK 20180308164851.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1809 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1809 Mutation of the Pancreatic Islet Inward Rectifier Kir6.2 Also Leads to Familial Persistent Hyperinsulinemic Hypoglycemia of Infancy [Elektronische Daten] [Pamela Thomas, Yuyang Ye, Elmer Lightner] Closure of ATP-sensitive potassium channels in pancreatic islet β-cells initiates a cascade of events that leads to insulin secretion. β-Cell ATP-sensitive potassium currents can be reconstituted by coexpression of the inward rectifier Kir6.2 and the sulfonylurea receptor (SUR), a member of the ATP-binding cassette superfamily. Mutations in SUR have been identified in individuals affected with familial persistent hyper-insulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder of glucose metabolism which is linked to chromosome 11p15.1 and characterized by unregulated secretion of insulin and profound hypo-glycemia. Because the Kir6.2 locus is within 5 kilobases (kb) of the SUR gene on chromosome 11p15.1 and it is a necessary member of the β-cell KATP channel, we considered Kir6.2 as a candidate gene for PHHI. We identified a homozygous point mutation in Kir6.2 in the genomic DNA of a child, severely affected with PHHI, from a consanguineous family. This mutation is predicted to disrupt the conservedα-helical second transmembrane (M2) domain of the inward rectifier by substitution of a proline for a leucine residue (L147P). Mutation of Kir6.2, like SUR, appears to lead to the PHHI phenotype suggesting that Kir6.2 is necessary, although not sufficient, for normal regulation of insulin release. © 1996 Oxford University Press Thomas Pamela Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA aut Ye Yuyang Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA aut Lightner Elmer Department of Pediatrics, University Medical Center, Tucson, AZ 85724, USA aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1809-1812 0964-6906 5:11<1809 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1809 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1809 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Thomas Pamela Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA aut NATIONALLICENCE 700 1- Ye Yuyang Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA aut NATIONALLICENCE 700 1- Lightner Elmer Department of Pediatrics, University Medical Center, Tucson, AZ 85724, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1809-1812 0964-6906 5:11<1809 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford