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 neonatal hyperinsulinaemic hypoglycemia. Linkage analysis in 15 families (12 Ashkenazi Jewish, 2 consanguineous Arab, 1 non–Jewish Caucasian) mapped HI to chromosome 11p14–15.1 (lod score = 9.5, θ=0 at D11S921 ). 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 secretion, represents a candidate gene for studies of other diseases of β–cell dysfunction including non–insulin–dependent diabetes mellitus (NIDDM).