Журнал клинических случаев

Androgen Receptor Gene Mosaicism in Partial Androgen Insensitivity Syndrome Patient Detected by Whole Exome Sequencing

Abstract

Zohor Azher, Mohammed Almatrafi, Abdullatif Almarashi and Abdulaziz Baazeem

Androgen insensitivity syndrome is the most frequent etiology of disorders of sex development in 46,XY individuals. It is characterized by evidence of feminization of the external genitalia at birth, abnormal secondary sexual development in puberty, and male infertility. It is an X-linked recessive disease caused by alterations in the androgen receptor (AR) gene, resulting in a spectrum of androgens resistance. The clinical phenotype can be classified into complete, partial, and mild forms. We report a male patient presenting clinical manifestations of partial phenotype: primary infertility, severe oligozoospermia, bilateral gynecomastia, decreased body hair distribution, and hypospadias. Whole exome sequencing (WES) revealed a hemizygous variant in the AR gene with a significantly reduced allele ratio compared with a normal hemizygous allele in male, which is consistent with somatic mosaicism. Mosaic variants in this gene are rare and are associated with incomplete gene dysfunction and subsequently mild or moderate phenotype. AR gene analysis is considered in infertile male patients with genital anomalies and features of under-virilization. Detection of somatic mosaicism is still a major technical challenge. However, WES offers an opportunity to detect lower levels of mosaicism more readily than other traditional methods. Identification of these mutations significantly impacts the diagnosis, management choices and genetic counseling for affected individuals.