A novel Arg615Ser mutation of androgen receptor DNA-binding domain in three 46,XY sisters with complete androgen insensitivity syndrome and bilateral inguinal hernia.

OBJECTIVE

To present clinical, genetic, biochemical, and molecular findings in a family with three sisters with complete androgen insensitivity syndrome (CAIS) and bilateral inguinal hernia.

DESIGN

Case report.

SETTING

Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad, India; Centre for Cellular and Molecular Biology, Hyderabad, India.

PATIENT(S): A family with four sisters of female phenotype, three of whom have CAIS and bilateral inguinal hernia. Their parents also were screened.

INTERVENTION(S): Chromosomal analyses by harvesting lymphocytes from peripheral blood sample; hormonal analysis from serum; gene sequencing.

MAIN OUTCOME MEASURE(S): Karyotype, testosterone, follicle-stimulating hormone, and luteinizing hormone evaluation, sex-determining region Y (SRY) and androgen receptor (AR) gene sequencing.

RESULT(S): In three sisters of karyotype 46,XY, we found a novel mutation of the single nucleotide transition C to A at position 2205 (GenBank accession number GU784857), resulting in amino acid interchange arginine to serine at codon 615 in exon 3 [R615S] (GenBank Protein_id ADD26779.1). The mother (46,XX) is a heterozygous carrier, and the fourth sister (46,XX) and father (46,XY) are normal.

CONCLUSION(S): We report a novel missense mutation in exon 3 of the androgen receptor gene. The nature of the mutation presented is in the highly conserved DNA-binding domain of the AR gene, implicating it in the phenotypes observed with severe undervirilization in three sisters.