Genetic Mechanisms of Sex Development and New Approaches

Sexual development is an extremely complex process. The disruptions in this process can evince as disorders of sex development (DSDs). DSDs are defined as “congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical and contain a wide phenotypic spectrum such as mild hypospadias, ambiguous genitalia, gonadal dysgenesis and sex reversal. Male or female development is genetically determined. Sex determination occurs as the bipotential gonad becomes either a testis or an ovary. Sexual differentiation together with the development of the gonad is maintained. Both internal and external genital organs are formed. These processes are influenced by the action of genes that were found by studies of DSDs patients. The molecular mechanisms underlying sex development have been clarified with amazing advances in genetic technologies. However, a specific molecular diagnosis is made in only 20% of patients. Today, this situation is likely to change with the development of genomic technologies. Studies of multigenic diagnostic screening and genome wide approaches such as array-comparative genomic hybridization and next-generation sequencing can be applied in the diagnosis of patients with DSDs. Herewith, more patients with DSDs will receive a definitive genetic diagnosis and prognostic prediction and long-term management will improve. This presentation will cover genetic mechanisms of sex development and current approaches in detail.