title: Genetics of the insulin receptor defect in a patient with extreme insulin resistance.
abstract: A patient with extreme insulin resistance (leprechaun/Ark-1) had an 80-90% decrease in the number of insulin receptors on her circulating monocytes. In contrast, while a normal number of insulin receptors was expressed on the surface of Epstein-Barr (EB) virus-transformed lymphocytes from the patient, the receptors had decreased sensitivity to changes in temperature and pH. The father, who had a moderate degree of insulin resistance, resembled the patient in that his monocytes had a 60-80% decrease in the number of insulin receptors. Binding to the father's EB virus-transformed lymphocytes was normal. The mother was normally sensitive to insulin and had a normal number of insulin receptors on her circulating monocytes. In contrast, insulin receptors on the mother's EB virus-transformed lymphocytes were qualitatively abnormal, closely resembling the daughter's cultured cells. These observations suggest that each parent has transmitted a different genetic defect to the patient. When both mutations coexist in the same individual, they fail to complement, but, rather, result in extreme insulin resistance.
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004700:Endocrine System Diseases / Q000235:genetics / Q000378:metabolism; D005145:Face / Q000002:abnormalities; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
chemical_list: D007328:Insulin; D011972:Receptor, Insulin