A Point Mutation Inactivating the Sulfonylurea Receptor Causes the Severe Form of Persistent Hyperinsulinemic Hypoglycemia of Infancy in Finland

摘要

Mutations in genes encoding the ATP-regulated potas- sium (K_ATP) channels of the pancreatic β-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). We collected all cases of PHHI diagnosed in Finland between 1983 and 1997 (n=24). The overall incidence was 1:40, 400, but in one area of Central Finland it was as high as 1:3, 200. Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster con- firmed linkage to the 11p region. Sequence analysis revealed a novel point mutation in exon 4 of SUR1, pre- dicting a valine to aspartic acid change at amino acid 187 (V187D).