Identification of the Rare Ala871Glu Mutation in the Androgen Receptor Gene Leading to Complete Androgen Insensitivity Syndrome in an Adolescent Girl with Primary Amenorrhea

Abstract

Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols. © 2022 by the authors.