Mutations of the androgen receptor coding sequence are infrequent in patients with isolated hypospadias.

Androgen receptor defects can cause severe hypospadias. To examine the possibility that androgen receptor defects are a common cause of such deficiencies, we have determined the coding sequence of the androgen receptor gene in nine patients with severe hypospadias. The analysis of the androgen receptor coding sequence predicts a normal amino acid sequence for the androgen receptor of eight of the nine patients, indicating that the observed defects in virilization are infrequently caused by mutations of the open-reading frame of the androgen receptor. These findings demonstrate the importance of family history and endocrine studies in identifying patients likely to harbor coding sequence mutations in the androgen receptor gene, and they serve to focus attention on other genes that may influence androgen action in this group of patients.