A 42-year-old female proband with complete AIS (CAIS) underwent genetic and clinical evaluation. Phenotypically female, she presented with primary amenorrhea, absent internal genitalia, and cardiomyopathy. Family history revealed three similarly affected sisters and a young granddaughter. Genetic analysis was performed through clinical exome sequencing and Geneyx Analysis platform, which performed variant annotation and prioritized phenotype-based candidate genes.

Genetic examination of the proband and her affected sister confirmed a 46,XY karyotype with no chromosomal abnormalities and the presence of the SRY locus, while their healthy niece exhibited a 46,XX karyotype. The AR c.2117A>G (p.Asn706Ser) variant was found in hemizygosity in the proband as well as in her affected sister, and in heterozygosity in their 46,XX niece.  Systematic review of the AR c.2117A>G variant revealed 19 cases worldwide, all presenting with CAIS and female phenotypes.

In summary, this study highlights a familial case of CAIS caused by the AR c.2117A>G variant, identified in two 46,XY siblings and their 46,XX heterozygous unaffected niece. Early diagnosis is critical, as CAIS is often misdiagnosed or delayed. Genetic counseling is essential to guide management, reproductive planning, and family risk assessment. This study reinforces the importance of genetic testing in AIS and provides valuable insights for multidisciplinary care and genetic counseling in affected families.