The Genetics and Disorders of Sexual Development

Sex determination in mammals is different, as a single bipotential gonad can develop either into a testes or an ovary. If this genetic process which is largely complex gets disrupted during development of a human being it can lead to disorders of sex development. There are two separate processes by which sex development takes place namely i) sex determination whereby the bipotential gonad forms either a testes or ovaries and sex differentiation of internal and external genitalia along with extragonadal tissues like the brain. DSD’s may occur due to different genetic lesion pathways. In this review we have concentrated in details of various genetic pathways causing DSD’s and signal transduction pathways by which various manifestations of gonadal forms like gonadal dysgenesis to ovotestis and genital forms from mild hypospadias or clitoromegaly to ambiguous genitalia phenotype may result. Here we do not touch on sex differentiation of internal genitalia and external genitalia. Keywords: DSD’s; Genetics; Signal Transduction System; Ambiguous Genitalia; Gonadal Dysgenesis; Ovotestis; SRY related high mobility group box (Sox) transcription factors have emerged in the animal kingdom to help cells maintain stemness, commit to a specific lineage, proliferate or die. Encoded by 20 genes in humans and mice they show a highly conserved high-mobility group boxdomain, which was originally identified in SRY, the sex determining region on the Y chromosome. This has derived from a high mobility group domain characterized of chromatin associated proteins. HMG (high mobility group) non histone chromosomal proteins include the AT hook, HMGN, and HMG domain families . Members of the Sox SRY (Sex determining region on the Y chromosome) related HMG box family of chromatin remodelling factors play important development roles. SRY plays a key role in mammalian sex determination as determined by the fact that 15% of all XY sex reversal individuals carry mutations in SRY.