XP DUPLICATIONS AND SEX REVERSAL

Male to female sex reversal has been observed in individuals with dupl ications of the short arm of the X chromosome. The study of Xp duplica ted patients demonstrated that sex reversal results from the presence of two active copies of the DSS (dosage sensitive sex reversal) locus. A double dosage of DSS disrupts testis formation whereas its absence is compatible with a male phenotype, suggesting a role for DSS in ovar ian development and as a link between ovary and testis formation. DSS was localized to a 160 kb region of Xp21, overlapping the adrenal hypo plasia congenita locus. The search for expressed sequences in the DSS critical region led to the identification of two types of genes: the D AM family and DAX-1, an atypical member of the nuclear receptor superf amily. Although no function is currently known for DAM genes, function al deficiency for DAX-1 has been shown to be responsible for adrenal h ypoplasia congenita and hypogonadotropic hypogonadism. The search for the DSS gene(s) is still open and both the DAM genes and DAX-1 represe nt DSS candidate genes.