Molecular characterization of the androgen receptor gene in boys with hypospadias

Development of male external genitalia is dependent on androgens, and karyotypic males lacking appropriate levels of androgens or functionally normal receptors may show abnormal virilization. Mutations in the androgen receptor gene cause abnormal receptor function and diverse mutations may be associated with heterogeneous clinical signs of androgen insensitivity. In this study, we have searched for the existence of androgen receptor gene mutations carried by some patients with hypospadias. Genomic DNA samples from peripheral blood leucocytes from 21 patients with different degrees of hypospadias were studied. Analysis of the androgen receptor gene was performed by exon-specific amplification using polymerase chain reaction, single strand conformation polymorphism analysis, and direct genomic sequencing. Although a silent polymorphism was identified in exon 1 of the androgen receptor gene, the majority of patients studied (20/21) did not carry androgen receptor gene mutations. One patient with severe hypospadias and bilateral cryptorchidism was found to carry a point mutation in exon 8. We conclude that mutations in the androgen receptor gene may be carried by subset of patients with genital ambiguity presenting primarily with hypospadias, but this is not the underlying cause in the majority of cases. Characterization of this genetic defect may be important for classification and subsequent conservative therapeutic approaches for these patients.