Complete Androgen Insensitivity Syndrome due to Mutations in the DNA-Binding Domain of the Human Androgen Receptor Gene

This study includes cytogenetics, hormonal, molecular, and bioinformatics analysis including sequencing of theSRY (sex-determining region Y) andAR genes. Mutational analysis in the first case of primary amenorrhea revealed a novel nucleotide substitution (IVS2-2A>G) in the second intron of theAR gene. The mutation is located in the acceptor splice site (2 nucleotides before exon 3) and caused skipping of exon 3 and formation of an abnormal protein. The second mutation (g. 98762_98764delTCT) was identified in a case of oligoamenorrhea and caused the deletion of 1 amino acid (p.#x2206;Phe583). Both identified mutations were located in the conserved P-box region of the DNA-binding domain which is responsible for base-specific contacts with the DNA major groove. Furthermore, a hormonal imbalance was also noticed in both cases with high levels of gonadotropins like FSH and LH in both cases. The present study concluded that both identifiedAR mutations are predicted to either abolish or decrease the binding ability of the AR to androgen response elements of its downstream genes.Sex Dev
Source: Sexual Development - Category: Biology Source Type: research