Mutations in the Sulfonylurea Receptor Gene in Familial Persistent Hyperinsulinemic Hypoglycemia of Infancy

作者：Pamela M. Thomas, Gilbert J. Cote, Nelson Wohllk, Bassem R. Haddad, Puthenpurackal M. Mathew, Wolfgang Rabl, Lydia Aguilar‐Bryan, Robert F. Gagel, Joseph Bryan · 发表于：Science · 年份：1995 · DOI：10.1126/science.7716548 · 被引用次数：818 · 研究领域：Hyperglycemia and glycemic control in critically ill and hospitalized patients、Pancreatic function and diabetes、Diabetes Management and Research

Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion, is linked to chromosome 11p14-15.1. The newly cloned high-affinity sulfonylurea receptor (SUR) gene, a regulator of insulin secretion, was mapped to 11p15.1 by means of fluorescence in situ hybridization. Two separate SUR gene splice site mutations, which segregated with disease phenotype, were identified in affected individuals from nine different families. Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide binding domain of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene.