The mastermind-like domain-containing 1 gene (<i>MAMLD1</i>, formerly <i>CXorf6</i>) is a new candidate gene and its mutation has been shown in some cases of 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.
These findings suggest that the CXorf6 mutations cause hypospadias primarily because of testicular dysfunction and resultant compromised testosterone production around that period, and provide useful information for the molecular network involved in fetal testosterone production.
These findings suggest that the MAMLD1 mutations cause hypospadias primarily because of compromised testosterone production around the critical period of sex development, and provide useful information for the molecular network involved in fetal testosterone production.
The transactivation function of the variant MAMLD1 proteins was quantified by the luciferase method.TWO NEW MUTATIONS WERE IDENTIFIED: p.S143X (c.428C>A) in a patient with scrotal hypospadias with microphallus and p.P384L (c.1151C>T) in a patient with penile hypospadias with microphallus.
Mastermind-like domain containing 1/chromosome X open reading frame 6 mutation and activating transcription factor 3 variants have been shown to be associated with the incidence of isolated hypospadias.
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.
Based on odds ratio at 95% CI, Z Statistic and Significance Levels, STS gene-rs17268974 was associated with Penile-Hypospadias and 9-SNPs [seven-SNPs (rs5934740; rs5934842; rs5934913; rs6639811; rs3923341; rs17268974; rs5934937)] of STS gene; rs7562326-SRD5A2 and rs1877031-STARD3 were associated with penoscrotal-hypospadias.
Mutations in the NR5A1 gene, which encodes the steroidogenic factor 1 (SF1), are responsible for different phenotypes of disorders of sex development (DSD), such as bilateral anorchia and hypospadias.
We provide new evidence of this involvement, describing a novel heterozygous non-sense NR5A1 mutation in a 46,XY-DSD with polysplenia female proband and her father, who had hypospadias and asplenia.
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.
Here, we report on male siblings with hypospadias and their asymptomatic father in whom we identified a heterozygous NR5A1 mutation of c.910G>A, p.E304K.
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.