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.
The results imply that CNVs in the AZF region and SRY are not associated with the risk of hypospadias in the Japanese population, although the pathogenicity of the AZF-linked simple duplication remains to be elucidated.
The father of the three children presented with hypospadias; cryptorchidism; testicular seminoma and oligoasthenozoospermia, an association termed testicular dysgenesis syndrome (TDS); and the SRY mutation in a mosaic state in the peripheral blood and the tumor.
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.
We report on a patient with 46, XY chromosomes, presence of the "sex-determining region of Y chromosome" (SRY) gene, scrotal gonads, fallopain tubes, uterus, vagina, and ambiguous genitalia with a penisoid, perineal hypospadia and sinus urogenitalis.
Molecular studies revealed Yp sequences in two individuals (ZFY+ SRY+) with different phenotypes, a third one presented with a smaller segment of Yp (ZFY- SRY+) and complete virilization, while the remaining three were Y-negative and showed hypospadias.