Objective: To study the androgen receptor gene in a large kindred with complete androgen insensitivity syndrome and positive receptor-binding activity. Design: Enzymatic amplification coupled with single strand conformation polymorphism and DNA sequencing were used. Results: In all the affected members, single strand conformation polymorphism showed a mobility shift in exon 2, suggesting a sequence alteration. Sequencing identified a valine into phenylalanine substitution at position 581 in the first zinc finger of the DNA-binding domain. Conclusion: This valine 581 is conserved in all nuclear receptors and has an important role for the recognition of the androgen response elements by the activated androgen receptor. This amino acid substitution has not been previously described in the androgen receptor in patients with androgen insensitivity syndrome. Moreover, single strand conformation polymorphism allowed determination of the generation in which the mutation appeared and performance of carrier diagnosis in this family.
Lumbroso, S., Lobaccaro, J. M., Belon, C., Martin, D., Chaussain, J. L., & Sultan, C. (1993). A new mutation within the deoxyribonucleic acid-binding domain of the androgen receptor gene in a family with complete androgen insensitivity syndrome. Fertility and Sterility, 60(5), 814–819. https://doi.org/10.1016/S0015-0282(16)56281-5