Objective: Different molecular factors have been identified as being associated with isolated or syndrome-associated forms of hypospadias. Nevertheless, the etiology of hypospadias is unknown in 70% of cases. As mutations in the homeobox gene A13 (HOXA13) were all found to be associated with hypospadias in affected males, some types of mutation may solely lead to the isolated form. Moreover, mutations in the Wilms' tumor suppressor gene WT1 have been found in patients with hypospadias without evidence of a Wilms' tumor and, therefore, its recently identified associated protein (WTAP) may be a further candidate gene for the genesis of hypospadias.
Material and methods: A total of 37 patients affected with different forms of isolated hypospadias were analyzed for mutations in their HOXA13 and WTAP genes.
Results: With the exception of two novel WTAP polymorphisms, no mutations could be observed.
Conclusions: There seems to be no evidence that isolated hypospadias is commonly caused by mutations in HOXA13 or WTAP genes.