RAPID DETECTION OF A MUTATION HOT-SPOT IN THE HUMAN ANDROGEN RECEPTOR

Mutations of the human androgen receptor gene may disturb sexual devel opment in males, and are inherited as an X-linked recessive trait. The vast majority of the mutations are familial. We have identified a lar ge kindred with complete androgen insensitivity syndrome (CAIS) withou t detectable androgen-binding in genital skin fibroblasts. A single nu cleotide substitution (C-to-T transition) was identified, resulting in an Arg(855) to CYS in the androgen binding domain. To date, four inde pendent CAIS families have been reported with this specific mutation t hat coincides with the propensity of cytosines at CpG dinucleotides to methylate. An allele-specific oligo-nucleotide assay was developed th at allowed for the rapid and specific identification of this mutation hot-spot in individuals with androgen receptor insensitivity syndromes .