Genetic variants and molecular profiling of 46,XY gonadal dysgenesis using whole-exome sequencing.

Background: More than 60% of cases of 46,XY gonadal dysgenesis (GD), a condition classified as a disorder of sex development (DSD), remain unexplained, which is due to high genetic and clinical heterogeneity. Whole-exome sequencing (WES) is an efficient primary genetic diagnostic method; specifically, the use of WES in patients with 46,XY GD to explore the underlying genetic variants of the disorder may help us gain a deeper understanding of the pathogenesis and phenotype-genotype correlation of 46,XY GD. Methods: We performed WES and pedigree studies to investigate the underlying genetic etiology of patients with 46,XY GD (six patients and six familial controls). The variants were confirmed via Sanger sequencing, and detailed functional prediction of the discovered genetic variants was conducted. Furthermore, we performed Results: We identified three novel pathogenic variants in Conclusion: The N-ZF domain may play an exclusive role in the mechanism of GATA4 in the pathogenesis of 46,XY GD; therefore, this domain may be an interesting topic for future investigation. This study enhances our understanding of the genetic etiology and pathogenesis of 46,XY GD, which may aid in the diagnosis and intervention of this disorder.