Detection of an Alteration in the Insulin-Receptor Gene in a Patient with Insulin Resistance, Acanthosis Nigricans, and the Polycystic Ovary Syndrome (Type A Insulin Resistance)

SEVERE insulin resistance is the central metabolic feature of a number of clinically diverse syndromes,1 including the type A syndrome (young female patients with insulin resistance, acanthosis nigricans, and virilization),2 leprechaunism,3 the Rabson–Mendenhall syndrome,4 and lipoatropic diabetes.5 A reduced expression or function of insulin receptors has been demonstrated in freshly obtained cells from a number of patients with these diseases.2 , 6 7 8 9 The existence of familial clusterings and the presence of defects in cultured cell lines7 , 10 11 12 have led to the view that receptor defects in these disorders may be primary. The cloning of the complementary DNA (cDNA) of the normal human insulin . . .