Objective: To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic testing and to offer carriership testing in female relatives should a disease-causing mutation be found.
Design: Case report.
Setting: University hospital.
Patient(s): Caucasian family in which two sisters were clinically diagnosed with CAIS during childhood.
Intervention(s): Molecular genetic testing of the androgen receptor (AR) gene.
Main outcome measure(s): Genetic counseling in affected and unaffected female family members.
Result(s): Identification of a novel mutation in exon 1 of the AR gene, c.118delA. This frameshift mutation (p.R40fs174ter) is located in the N-terminal transactivation domain and leads to a predicted truncated protein of 173 amino acids with loss of the major part of the N-terminal transactivation domain, and the DNA-binding and ligand-binding domain. Segregation analysis showed carriership of this mutation in the mother and two sisters.
Conclusion(s): In agreement with functional studies of other AR gene mutations located in the N-terminal transactivation domain, this novel mutation c.118delA is presumed to result in a complete loss of AR function and to be associated with CAIS. Our study extends the spectrum of exon 1 mutations in the AR gene leading to CAIS. Molecular genetic testing of CAIS is recommended not only for diagnostic purposes in affected individuals but also for carriership testing and genetic counseling in unaffected female family members.