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

TLDR

Familial persistent hyperinsulinemic hypoglycemia of infancy is an autosomal recessive disorder marked by unregulated insulin secretion and linked to chromosome 11p14‑15.1. The high‑affinity sulfonylurea receptor gene, a key regulator of insulin secretion, was mapped to 11p15.1 and two splice‑site mutations segregating with disease were identified in nine families. These mutations caused aberrant RNA processing and disrupted the second nucleotide‑binding domain of SUR, resulting in abnormal insulin secretion in PHHI.

Abstract

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.