Hyperproinsulinemia in a family with a proposed defect in conversion is linked to the insulin gene.
Two previously described pedigrees with familial hyperproinsulinemia have elevated proinsulin conversion intermediates resulting from amino acid substitutions in the proinsulin molecule. In contrast, a third family with elevated levels of an apparently normal proinsulin molecule may have a defect in the converting process. To determine if the defect in this family lies in the insulin gene region, we used restriction fragment length polymorphisms adjacent to the insulin gene to examine cosegregation with hyperproinsulinemia. We demonstrate linkage of hyperproinsulinemia and the insulin gene in this family with a LOD score of 1.8, suggesting that the defect lies in or near the insulin gene. This method has wide applicability in determining whether hyperproinsulinemia or hyperinsulinemia is the result of defects at the insulin gene, and should permit the detection of new defects at or near this locus.
Elbein
S C
SC
Gruppuso
P
P
Schwartz
R
R
Skolnick
M
M
Permutt
M A
MA
D000483:Alleles; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011384:Proinsulin / Q000097:blood*
D007328:Insulin; D004247:DNA; D011384:Proinsulin; D004262:DNA Restriction Enzymes