MOLECULAR CHARACTERIZATION OF THE ANDROGEN RECEPTOR GENE IN BOYS WITHHYPOSPADIAS

Development of male external genitalia is dependent on androgens, and karyotypic males lacking appropriate levels of androgens or functional ly normal receptors may show abnormal virilization. Mutations in the a ndrogen receptor gene cause abnormal receptor function and diverse mut ations may be associated with heterogenous clinical signs of androgen insensitivity. In this study, we have searched for the existence of an drogen receptor gene mutations carried by some patients with hypospadi as. Genomic DNA samples from peripheral blood leucocytes from 21 patie nts with different degrees of hypospadias were studied. Analysis of th e androgen receptor gene was performed by exon-specific amplification using polymerase chain reaction, single strand conformation polymorphi sm analysis, and direct genomic sequencing. Although a silent polymorp hism was identified in exon 1 of the androgen receptor gene, the major ity of patients studied (20/21) did not carry androgen receptor gene m utations. One patient with severe hypospadias and bilateral cryptorchi dism was found to carry a point mutation in exon 8. We conclude that m utations in the androgen receptor gene may be carried by subset of pat ients with genital ambiguity presenting primarily with hypospadias, bu t this is not the underlying cause in the majority of cases. Character ization of this genetic defect may be important for classification and subsequent conservative therapeutic approaches for these patients.