Androgen insensitivity syndrome (AIS; Online Mendelian Inheritance in Man [OMIM; #300068]) is an X-linked recessive disorder caused by pathogenic variants in the androgen receptor (AR) gene located in the Xq11-q13 region. In this retrospective study of 30 patients with AIS, next-generation sequencing identified 24 variants in AR, including 20 missense, 1 nonsense, and 3 splice-site variants. Seven novel variants were detected in 8 patients. Of the 24 variants, 15 were classified as likely pathogenic, 8 as pathogenic, and 1 as of uncertain significance. Variants included 5 de novo and 24 familial cases. These AR variants were predominantly located in the functional domains, with the ligand-binding domain (LBD) harboring 10 variants, the DNA-binding domain (DBD) harboring 5 variants, the N-terminal domain (NTD) harboring 2 variants, and the hinge region (HR) harboring 1 variant. The highest variant detection rate occurred in exon 5 (11/30), followed by exon 3 (9/30). These findings advance our understanding of genotype including 20 missense, 1 nonsense, and 3 splice-site variants through the identification of 7 novel variants.

Keywords: 46,XY DSD; AIS; AR; disorder of sex development