MUTATIONS IN THE SULFONYLUREA RECEPTOR GENE IN FAMILIAL PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY

Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a n autosomal recessive disorder characterized by unregulated insulin se cretion, is linked to chromosome 11p14-15.1. The newly cloned high-aff inity sulfonylurea receptor (SUR) gene, a regulator of insulin secreti on, was mapped to 11p15.1 by means of fluorescence in situ hybridizati on, 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 bind ing domain of the SUR protein. Abnormal insulin secretion in PHHI appe ars to be caused by mutations in the SUR gene.