Abstract
We examined the insulin receptor gene in a 20-year-old woman with type A insulin resistance who presented with acanthosis nigricans and polycystic ovary.An oral glucose tolerance test showed a diabetic pattern and hyperinsulinemia.Resistance to exogenous insulin was evident. Insulin binding to fibroblasts and Epstein-Barr virus-transformed lymphocytes (EBTL) was within the normal range, but autophosphorylation and tyrosine kinase activity were reduced in partially purified insulin receptors from EBTL.We determined the nucleotide sequence for all 22 exons of the insulin receptor gene directly by the polymerase chain reaction.We demonstrated that the patient was heterozygous for a mutation substituting valine for glycine at codon 1008 in the tyrosine kinase domain.This mutation was the same as type A Hokkaido (Odawara et al.Science, 245, 66, 1989), but we could not find any relationship between the two families. The father was heterozygous for the same mutation and had an impaired glucose tolerance with mild hyperinsulinemia.The mother and two brothers had normal glucose tolerance.We conclude that the mutation in the tyrosine kinase domain caused dominant insulin resistance.
