PREMATURE TERMINATION MUTATION ((772)GLU-]STOP) IN THE HORMONE-BINDING DOMAIN OF THE ANDROGEN RECEPTOR IN A PATIENT WITH THE RECEPTOR-NEGATIVE FORM OF COMPLETE ANDROGEN INSENSITIVITY SYNDROME

We have characterized the androgen receptor in a Japanese infant with complete androgen insensitivity syndrome (or androgen resistance), and have investigated the molecular basis. Androgen binding was undetectable in cultured genital skin fibroblasts from this patient by whole-cell androgen receptor binding assay. Sequence analysis of the entire coding region of the androgen receptor gene from this patient revealed a single nucleotide substitution (G-->T) at nucleotide position 2676 in exon E (Or 5), resulting in conversion of glutamine codon (GAG) to amber stop codon (TAG) at amino acid position 772 within the hormone-binding domain of the androgen receptor. This premature termination mutation (or nonsense mutation), introducing a truncated androgen receptor that lacks most of its androgen binding capacity, is thought to cause the receptor-negative form of complete androgen insensitivity syndrome in this patient.