A novel androgen receptor gene mutation in a patient with congenital adrenal hyperplasia associated with penoscrotal hypospadias

Congenital adrenal hyperplasia (CAH) associated with penoscrotal hypospadias is a rare case of disorders of sex development. Here, we report clinical, genetic, biochemical, and molecular findings in a 2-year-old infant with CAH and penoscrotal hypospadias. Chromosomal analysis revealed 46,XX karyotype. Hormonal investigations indicated low levels of cortisol and elevated levels of testosterone, 17-hydroxyprogesterone, and androstenedione hormone. Molecular genetic testing of androgen receptor (AR) gene identified a novel homozygous missense mutation of single nucleotide transition G to A at position 2058 (GenBank accession number GU784855), resulting in amino acid interchange alanine to threonine at codon 566 in exon 2 (Ala566Thr) (GenBank Protein_id ADD26777.1). The nature of the mutation presented is in the highly conserved DNA-binding domain of the AR gene. The novel mutation identified in the rare genetic disorder provides additional support to the previously reported genotype-phenotype correlations, and our finding has expanded the spectrum of known mutations of the AR gene.