Furthermore, a Japanese boy with insulin resistance and acanthosis nigricans was found to be heterozygous for a mutation of the insulin receptor gene that resulted in the replacement of glycine-996 with valine in the ATP binding site of the receptor.
Acanthosis nigricans with high fasting insulin levels in the proband suggested severe insulin resistance and prompted INSR gene sequencing, which revealed the novel, heterozygous p.Phe1213Leu mutation in the patient and his family members.
By contrast, a larger group of insulin-resistant patients who were obese with hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) did not have a high probability of mutations in the insulin receptor.
Defects in the insulin receptor gene causing insulin resistance and AN are well recognized, but recent data in several other syndromes of this association, including lipodystrophic disorders, have identified causative defects in other pathways.
We examined the properties of a mutant insulin receptor (IR) with an Arg(252) to Cys (IR(R252C)) substitution in the alpha-subunit originally identified in a patient with extreme insulin resistance and acanthosis nigricans.
In addition to being a target for androgens the skin has abundant insulin receptors on the keratinocyte surface membrane and acanthosis nigricans is a common symptom of severe insulin resistance among patients with insulin receptor disorders.
We have used DGGE to screen for mutations in the insulin receptor gene in a family in which four of five daughters were affected by type A insulin resistance in association with acanthosis nigricans and hyperandrogenism.
A mutant insulin receptor gene lacking almost the entire kinase domain has been identified in an individual with type A insulin resistance and acanthosis nigricans.