Investigation of androgen receptor gene mutations in a series of 21 patients with 46,XY disorders of sex development

Aim: Androgen receptor (AR) gene mutations are the leading cause of 46, XY disorders of sex development (DSD) and are associated with varying degrees of androgen insensitivity. The aim of this study is to investigate AR gene mutations in 46, XY DSD patients with normal testosterone secretion, either normal or high testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2 gene analysis, collectively, suggestive of androgen insensitivity syndrome (AIS). Methods: We direct sequenced all eight exons of the AR gene in 21 index patients with varying degrees of undervirilization. Results: We detected AR gene alterations in five patients. In patients with complete AIS we found p.Val30Met in exon 1 and p.Gly689* in exon 4. One patient with partial AIS had p.Gln712Glu in exon 4. In two patients with partial phenotype, we found common p.Glu213Glu (c.639G>A) SNP, and an additional p.Ile817Ile (c.2451T>C) mutation was found in one of these two patients. Discussion: Despite the fact that T/DHT ratio is frequently used in diagnosis of AIS, lack of precisely determined cutoffs compromises correct diagnosis. Hence, depending on clinical and biochemical findings solely may delay correct diagnosis. Direct sequence analysis of the AR is essential for precise diagnosis of AIS.