The hypospadias phenotype was almost identical to that reported for the estrogen receptor α (ERα) knockout confirming that ERα is the predominant receptor for mediating estrogen action during development of the mouse penis.
Similar to single nucleotide polymorphism analysis, different ESR1 haplotypes were associated with risk of hypospadias in nonHispanic white and Hispanic subjects.
These findings suggest that the G allele containing variants of ESR1 XbaI and the G allele containing variants of ESR2 2681-4A>G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk.
We screened 60 boys with hypospadias for mutations in the coding regions of ESR1 and ESR2 genes, by denaturing high-performance liquid chromatography and automated sequence analysis.