Molecular analysis of the AR and SRD5A2 genes in patients with 46,XY disorders of sex development

The aim of this study was to assess the clinical and endocrinological features, and to analyze AR and SRD5A2 genes in patients with 46,XY disorders of sex development (DSD). This study included 20 patients from 19 families showing clinical features of 46,XY DSD. Molecular analysis was performed of the AR and SRD5A2 genes, as well as endocrinological evaluations, such as 17 alpha-hydroxyprogesterone, plasma renin activity, aldosterone, adrenocorticotropic hormone and hCG stimulation test. Out of 20 patients with 46,XY DSD, only one (5%) displayed androgen insensitivity syndrome (AIS), and four (20%) were 5 alpha-reductase deficient by mutation analysis. The patient with AIS revealed significant elevation of serum testosterone following hCG stimulation. The patient with 5a-reductase deficiency with a homozygous p.R246Q mutation had a low basal dihydrotestosterone level. The patient with p.Q6X/p.R246Q mutations showed a moderately elevated testosterone/dihydrotestosterone ratio following hCG stimulation. Endocrinological tests are not reliable for the etiological diagnosis of AIS and 5a-reductase deficiency due to variable reference ranges of hormonal profiles according to the age and the severity of the enzyme defect. DNA analysis may be employed as a tool for the early and precise diagnosis of patients with 46,XY DSD, and genetic counseling can be used for families at risk.