FAMILIAL HYPERINSULINISM MAPS TO CHROMOSOME-11P14-15.1, 30 CM CENTROMERIC TO THE INSULIN GENE

Familial hyperinsulinism (HI) is the most common cause of persistent n eonatal hyperinsulinaemic hypoglycemia. Linkage analysis in 15 familie s (12 Ashkenazi Jewish, 2 consanguineous Arab, 1 non-Jewish Caucasian) mapped HI to chromosome 11p-1415.1 (lod score = 9.5, theta = 0 at D11 S921). Recombinants localized the disease locus to the 6.6 cM interval between D11S926 and D11S928. In Jewish families, association (p=0.003 ) with specific D11S921/D11S419 haplotypes suggested a founder effect. This locus, which is important for normal glucose-regulated insulin s ecretion, represents a candidate gene for studies of other diseases of beta-cell dysfunction including non-insulin-dependent diabetes mellit us (NIDDM).