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Coronavirus Update:What patients and families need to know

The Children's National Research Institute

Gender-Based Biology

Etiology of Disorders/Differences of Sex Development

Disorders/Differences of Sex Development (DSD) are a spectrum of developmental conditions with complex overlapping phenotypes placing affected individuals at risk for life-threatening hormonal crises, infertility, cancer, sexual dysfunction, gender dysphoria and psychosocial distress. While at least 75 genes are known to cause these conditions in humans, each explains a small number of cases and a majority of patients remain undiagnosed. The team has used animal and cellular models, through candidate gene or genome-wide approaches, to identify new genes and validate novel pathogenic variants for several DSD conditions. The team identified 15 novel candidate genes and demonstrated that they are expressed in a sex-specific manner in the developing gonad, many under the control of the well-known sex-determining gene Sox9 (Barseghyan et al. 2018). To further validate these candidate genes, the team has now undertaken to clone variants of unknown clinical significance found in the genomes of patients with DSD into expression vectors to assay their effects on function of the proteins in vitro. The team is also developing a model of testicular (Sertoli) cell in culture using transdifferentiation to test gene function and variants directly in patient-derived cells.