A case of complete androgen insensitivity syndrome: genetic analysis of the family.

Besides many other factors, androgens play a role in expression of male phenotype. Androgen activity is mediated by androgen receptor (AR). After binding to androgen, AR translocates to nucleus and adheres to the regulatory regions of specific chromosomal DNA sequences (androgen response elements/ARE), to activate androgen dependent genes. The AR is encoded by the AR gene (Xq11–12). The gene is formed by 8 exons and 7 introns, spanning more than 90 kb. The functional domains are (a) exon 1 encoding the N-terminal domain (NTD) (1,586 bp); (b) exons 2 and 3 encode the DNA-binding domain (DBD) (152 and 117 bp); (c) the ‘‘hinge’’ region which binds the NTD and DBD consists of residues 628–669; (d) exons 4–8 encode the C-terminal ligand-binding domain (LBD), (131–288 bp). The C-terminus of the LBD mediates the hormone-dependent transcription. Mutations in the LBD region of AR perturb the conformation of the helix. The mutant AR is unable to efficiently bind to dihydrotestosterone (DHT) and to transactivate AREs [1]. Mutations in the AR gene leading to disordered AR function results in different forms of X-linked male pseudohermaphroditism, known as androgen insensitivity syndrome (AIS). This affects XY female individuals with normal androgen production and metabolism. AIS is present in 1:20,000–64,000 male births. The presence of variable phenotypic expression allows for the classification of AIS into complete androgen insensitivity (CAIS), partial androgen insensitivity (PAIS), and mild androgen insensitivity (MAIS). Approximately, 90 % of molecular defects in AR gene are single base point mutations, mostly missense mutations [2]. Here, we describe a familial case of CAIS presenting with similar mutations described across three generations. To the best of our knowledge and belief, ours is first such report citing this mutation in an Indian family.