A Novel Androgen Receptor Gene Mutation in a 46,XY Patient: Complete Androgen Insensitivity Syndrome

ABSTRACT Objective: Androgen insensitivity syndrome is the most common cause of 46,XY disorders of sex development (DSD). This condition is inherited from an X-linked recessive pattern, and the most common causes are inactivating mutations in the androgen receptor (AR) gene. The current study reports a novel AR gene mutation in an adolescent patient presenting with primary amenorrhea. Methods: A 16-year-old patient was admitted to our department with complaints of primary amenorrhea and a request for genetic counseling. The patient's medical history revealed that she underwent a bilateral inguinal hernia operation when she was 4 months old. The physical examination revealed that the external genitalia structure was totally consistent with a female phenotype; and according to the Tanner stages, breast and pubic hair development were stages 5 and 1, respectively. Karyotype analysis was reported to be 46,XY. Therefore, the diagnosis of complete androgen insensitivity syndrome (CAIS) was suspected, and the AR gene was sequenced. Results: AR gene mutation analysis revealed a novel hemizygous frameshift mutation (c.1629_1630insA; p.R544KfsX8) as the cause of the phenotype in this patient. Conclusion: This case report emphasizes that: (1) 46,XY DSD should be considered in the differential diagnosis of patients with a female phenotype presenting with bilateral inguinal hernia during the early infancy period, and (2) CAIS should be considered in the differential diagnosis of patients with female phenotype and breast development presenting with primary amenorrhea. Abbreviations: AIS = androgen insensitivity syndrome AMH = anti-Müllerian hormone AR = androgen receptor 17-β HSD = 17-β-hydroxysteroid dehydrogenase CAIS = complete androgen insensitivity syndrome DSD = disorders of sex development E2 = estradiol N = normal SRD5A2 = 5-alpha-reductase type 2