A unique point mutation in the androgen receptor gene in a family with complete androgen insensitivity syndrome

Objective: To further delineate the diversity of genetic alterations in the gene coding for the androgen receptor in individuals with the androgen insensitivity syndrome and to increase our understanding of the disease at the molecular level. Design: This was a prospective study in which genomic deoxyribonucleic acid (DNA) from individuals with androgen insensitivity were examined through the polymerase chain reaction and DNA sequencing analysis. Patients: Eleven complete and four individuals with partial androgen insensitivity syndrome were examined. Results: Exons two through eight were grossly intact in all study subjects. Nucleotide sequence analysis revealed that three of three related family members with complete androgen insensitivity had the same guanine to adenine base substitution in exon five of the steroid-binding domain. Conclusion: The subsequent alanine to threonine amino acid conversion may have resulted in a configurational change of the androgen receptor protein leading to complete androgen insensitivity. This precise alteration has not been previously identified in the human androgen receptor gene in patients with the androgen insensitivity syndrome.