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

Mol Cells. 1998 Dec 31;8(6):741-5.

Abstract

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

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgen-Insensitivity Syndrome / genetics*
  • Androgen-Insensitivity Syndrome / pathology
  • Androgens / metabolism*
  • Binding Sites
  • DNA / analysis
  • DNA / genetics
  • Female
  • Frameshift Mutation*
  • Humans
  • Male
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism

Substances

  • Androgens
  • Receptors, Androgen
  • DNA