Frame-shift mutation in hormone binding domain of human androgen receptor gene causes complete androgen insensitivity

Mutation of the human androgen receptor gene impairs normal sexual differen tiation and development in karyotypic males, resulting in a spectrum of ext ernal genital phenotypes ranging from complete female to nearly complete ma le. The androgen insensitivity syndrome (AIS) is an X-linked disorder in wh ich genetic males fail to undergo normal fetal masculinization or pubertal virilization, PCR amplification of AR exons followed by SSCP analysis was p erformed with the genomic DNA of a patient having complete AIS, Mutation wa s observed at the exon E, where a single nucleotide deletion of T at the nu cleotide 3286 was observed by cyclic sequencing. A single base deletion in Exon E in the hormone binding domain causes a frame-shift mutation, which l eads to changes in the open reading frame, and causes the early termination of AR synthesis. The structural change of the hormone binding domain and A R might cause an insensitivity to the androgen thus leading to AIS.