Molecular advances have helped elucidate the genetics of various disorders of sex differentiation. Consensus now exists that SRY (sex-determining region Y) is identical to TDF (testis-determining factor). The SRY gene is comprised of two open reading frames of 99 and 273 amino acids, respectively; the key sequence involves an HMG (high mobility group) box that shares characteristics with other DNA binding sequences. The Y chromosome also contains a locus or loci integral for spermatogenesis long postulated to reside on Yq, located in the nonfluorescent region. More recently this locus has been called DAZ (Deleted Azoospermia). The X chromosome has gained added relevance for testicular development because Xp has been shown to contain a region that if duplicated suppresses testicular development despite presence of SRY. Autosomal genes are also important for testicular differentiation. Foremost is the gene causing campomelic dysplasia and XY sex reversal located on 17q24.3-q25; other autosomal regions that could influence testicular development include 3p, 9p, 10q, and 11p. Genes responsible for many forms of male pseudohermaphroditism have also been localized and dissected molecularly-androgen insensitivity, enzymes in the adrenal biosynthetic pathway, Leydig cell aplasia, and persistence of müllerian derivatives in men. With rare exceptions, these disorders are characterized by molecular heterogeneity. No single mutation is universally observed in affected siblings.
