The unique features of SRD5A2 defects were p.R246Q (most prevalent) and p.G196S could be mutational hotspots, dual gene defects (p.A596T in AR and p.G196S in SRD5A2) in a patient with hypospadias and novel 8 nucleotide deletion (exon 1) found in a patient with perineal hypospadias.
A total of 395 boys with hypospadias were prospectively screened for a family history with a standardized questionnaire, extensive clinical description, family tree and sequencing of AR, SF1, SRD5A2 and MAMLD1.
The significant positive association of mRNA expression level and the negative association of methylation level of the SRD5A2 gene with the mRNA expression levels of CYP1 family genes in the preputial tissue seem to indicate the chemical exposure of patients with hypospadias.
Eight different SRD5A2 mutations were detected in 15 patients with posterior hypospadias (60%, 15/25), including six previously described mutations (p.Q6X, Q71X, p.L20P, p.G203S, p.R227Q, and p.R246Q) and two novel mutations (p.G196R and p.L73Pfs<sup>∗</sup>17).
In the present study, we investigated 13 haplotype tagging single nucleotide polymorphisms (SNPs) covering the steroid-5-alpha reductase (SRD5A2) and androgen receptor(AR) gene region, respectively, in a cohort consisting of 260 individuals with mild hypospadias and 77 with severe disease, in addition to 471 healthy male controls.
As androgens have a significant role in the development of the male urethra, we sought to investigate the association between 2 functional polymorphisms, CYP17-A1/A2 and SRD5A2-V89L, which are involved in the biosynthesis of testosterone and dihydrotestosterone, respectively, in relation to hypospadias.
Assessment of hypospadias including its severity and HSD17B3 and SRD5A2 genes using DNA blood samples: allele and genotype distribution of single nucleotide polymorphisms in these two genes in cases and controls.
Steroid 5-alpha-reductase 2 deficiency is an autosomal recessive disorder with clinical spectrum ranges from a male phenotype with hypospadia to a female phenotype with normal wolffian structures.