ANDROGEN RECEPTOR GENE-MUTATIONS ARE RARELY ASSOCIATED WITH ISOLATED PENILE HYPOSPADIAS

Purpose: Hypospadias has no known single etiology but it has been link ed to androgen insensitivity caused by mutations of the androgen recep tor gene. The purpose of this study was to search ibr such mutations i n cases of various degrees of isolated hypospadias to determine whethe r such an association exists and, if so, with any particular anatomica l subgroup. Materials and Methods: Isolated deoxyribonucleic acid from the penile tissue of 40 patients undergoing reconstructive surgery wa s screened for mutations of the coding regions of the androgen recepto r gene using single strand conformational polymorphism analysis. In ca ses with abnormal single strand conformational polymorphism findings s equence analysis of the deoxyribonucleic acid was performed to define the mutation. Results: A missense mutation of exon 2 of the androgen r eceptor gene was noted in 1 patient with isolated distal penile shaft hypospadias. Sequence analysis revealed that the mutation changed amin o acid residue 546 from proline to serine. No abnormalities were detec ted in the other 39 patients. Conclusions: Isolated distal shaft hypos padias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.