We used the AFP and free beta-HCG levels separately to predict fetuses with hypospadias, and the AUCs were 0.644 (95% Confidence interval (CI): 0.5500.737, P = .005) and 0.659 (95% CI: 0.5650.752, P = .002), respectively.
In the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were significantly associated with risk of CO. Interaction analysis of the positive SNPs using multifactor dimensionality reduction demonstrated that synergistic interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction accuracy for CO (P=0.011) and that between rs2069521 and rs2278705 had 69.98% prediction accuracy for HS (P=0.001) in JPN population.
Although androgens are clearly critical for penile development, defects in androgen metabolism and/or the androgen receptor explain only a small subset of cases of hypospadias.
The genes of penile development (HOX, FGF, Shh) and testicular determination (WT1, SRY) and those regulating the synthesis [luteinizing hormone (LH) receptor] and action of androgen (5alpha reductase, androgen receptor) can cause hypospadias if altered.
This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life.
These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11-17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology.
We identified patients from the Cambridge Disorders of Sex Development Database with the AR substitutions: Phe754Ser with microphallus without hypospadias and Asp690Val with complete AIS.
Endogenous endocrine abnormalities identified so far include testosterone biosynthesis defects, 5alpha-reductase type 2 mutations, and androgen receptor mutations (the rarest cause, even in cases of severe hypospadias).
Co-regulators of the androgen receptor start being acknowledged as possible candidates for hormone-resistance instances, which could account for hypospadias.
The correlation between the level of androgen receptor mRNA expression and the penile size was almost statistically significant only in hypospadias patients (r=0.47; p=0.053).
To test this hypothesis we measured estrogen and androgen formation in two brothers with perineoscrotal hypospadias and severe gynecomastia (the Reifenstein phenotype) due to a mutation that impairs androgen receptor function.
To examine the possibility that androgen receptor defects are a common cause of such deficiencies, we have determined the coding sequence of the androgen receptor gene in nine patients with severe hypospadias.
Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.
Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias.