General Medical Information

Autosomes

Joe Leigh Simpson

Autosomal loci are pivotal for testicular differentiation. Several autosomal regions have generated special interest: 9p, 10q, 11p, and 17q. The gene responsible for campomelia dysplasia and XY gonadal dysgenesis (sex reversal) is localized to 17q24.3®q25.1). Pathogenesis involves SOX9. Like SRY, SOX9 is DNA binding and has an HMG box; however, analysis of SOX9 in campomelia dysplasia has not always shown correlations with sex reversal, suggesting genetic heterogeneity. The Wilms’ tumor suppressor gene (WT-1), located on 11p, is associated with gonadal and genital abnormalities (male pseudohermaphroditism); however, WT-1 apparently is rarely, if ever, deleted in XY gonadal dysgenesis. Deletions of 10q also have been associated with XY gonadal dysgenesis. No candidate gene is identified.

An autosomal region that seems pivotal could be 9p. Approximately 70% of 46,XY cases with del(9p) show sex reversal, and an increasing number of XY gonadal dysgenesis cases show this deletion. Vegetti found that five of nine cases of XY gonadal dysgenesis showed 9p deletions.

Other syndromes deleteriously affecting testicular differentiation are heritable and act in autosomal fashion, but they have not been localized to a specific chromosomal region. These include agonadia, rudimentary testes syndrome, and the syndrome of germ cell hypoplasia in both males (germinal cell aplasia) and females (streak gonads). In addition, autosomal genes must influence XX true hermaphroditism. Familial aggregates occur, and SRY usually is not present.