[Molecular sex determination. Significance in the diagnosis of gonadal pathologies]

Sex differentiation follows two steps: sex determination where gender follows from the development of the embryonic gonads such as testes or ovaries and sex differentiation leading to the formation of internal and external genitalia. In man, testis determination is dependent on SRY gene (sex region of Y) on the short arm of Y chromosome (Yp11.3). It has an open reading frame that encodes a 220 aa protein with a 80 aa motif related to HMG box. These sequences have been shown to mediate DNA binding. Recently, a DSS locus (Dosage Sensitive Sex-Reversal) has been isolated on Xp21. This gene could be involved in ovaric determination. Moreover, it has been shown that SRY gene expression activates a regulatory pathway that leads to the expression of MIS (Mullerian Inhibiting Substance). Finally, the molecular genetic techniques have provided the tools for the analysis of these genes in patients with gonadal dysgenesis. The information obtained together with phenotype and cytogenetic data has established important correlations of diagnosic value.