Acanthosis nigricans-insulin resistance Type A syndrome: analysis of restriction fragments length polymorphisms at the insulin receptor locus

We have identified two sisters (12 and 17 years old) affected by acanthosis nigricans-insulin resistance (AN-IR) type A syndrome and Type 2 (non-insulin-dependent) diabetes mellitus. They presented with acanthosis nigricans, marked hyperinsulinaemia and severe insulin resistance, Type 2 diabetes, no antibodies to the insulin receptor, obesity and virilisation without other endocrine diseases. Both parents and paternal grandmother had Type 2 diabetes. In AN-IR type A syndrome a primary defect of insulin receptor is supposed. The availability of cloned DNA (cDNA) for the human insulin receptor allows examination of the possible role of this gene in this syndrome. Therefore we analysed restriction fragments length polymorphisms (RFLP) for the insulin receptor gene in different members of this family, including diabetic and non diabetic subjects. DNA extracted from white blood cells was digested by seven restriction enzymes, analysed by Southern blotting technique, using a eDNA probe for the insulin receptor of 4.2 kilobases. Insulin receptor DNA fragments appeared the same in all the examined subjects. No association of any RFLP was noted with the syndrome. Therefore, in this family, RFLPs for the insulin receptor gene were uninformative in evaluating the role of this gene in AN-IR type A syndrome, nevertheless the obtained results exclude its marked alterations in the investigated patients