A substitutional mutation in the DNA binding domain of the androgen receptor causes complete androgen insensitivity syndrome

DNA analysis of the androgen receptor gene in a patient with complete andro gen insensitivity syndrome identified a substitutional mutation (tyrosine c onverted to cysteine at position 571) in the DNA binding domain. In vitro t ransfection experiments with the patients' androgen receptor gene, indicate d normal expression of the androgen receptor in transfected COS-7 cells com pared to the wild type gene. There was also no evidence of impaired thermal stability of the 5 alpha-dih ydrotestosterone-androgen receptor complex. However, the capacity of the an drogen receptor to activate target gene transcription was found to be compl etely disrupted in a luciferase assay. These results confirmed that only on e substitutional mutation in the DNA binding domain was related to the path ogenesis of the complete androgen insensitivity syndrome.