A Novel Mutation in the Androgen Receptor Gene of Female Patients with 46,XY Karyotype.

BACKGROUND: In this study, we aimed to analyze androgen receptor (AR) gene mutations in five members of a family with complete androgen insensitivity syndrome (CAIS). METHODS: Peripheral blood samples were collected from the proband and four relatives (mother, sister, and two aunts). Cytogenetic imaging and chromosomal analysis were per-formed to elucidate the genetic basis of the condition. Clinical Exome Sequencing (CES) was conducted to identify candidate variants, which were subsequently validated using Sanger sequencing. Evolutionary conservation analysis was performed for the identified AR gene mutation. RESULTS: Our analyses revealed that the proband, sister, Aunt I, and Aunt II exhibited a 46,XY karyotype and carried the SRY gene. The mother, however, had a 46,XX karyotype, and did not carry the SRY gene, confirming X-linked recessive inheritance of the condition. CES results demonstrated that the proband, sister, Aunt I, and Aunt II harbored a hemizygous c.2246C>T (p.Ala749Val) mutation, while the mother carried this mutation in a heterozygous state. The presence of this mutation was confirmed by Sanger sequencing. Evolutionary conservation analysis indicated that the mutation is conserved among vertebrates. CONCLUSION: in conclusion, we identified a novel missense mutation (c.2246C>T) in the AR gene in five members of a CAIS-affected family, which has not been previously reported in the literature.