23 - PAX2 and Renal-Coloboma Syndrome

Abstract

Mutations in the PAX2 gene cause renal-coloboma syndrome (RCS), a rare syndrome characterized by optic nerve colobomas and renal abnormalities. PAX2 mutations are associated with oligomeganephronia (primary renal hypoplasia). Approximately 63% of patients with RCS have renal hypoplasia in addition to optic nerve colobomas, with or without additional abnormalities, including vesicoureteric reflux (VUR), high-frequency hearing loss, central nervous system (CNS) anomalies, or genital anomalies. Nine different PAX2 mutations have been identified to date, which cause either RCS or oligomeganephronia. Several animal models of mutations in PAX2 homologous sequences are developed including Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mice. One murine PAX2 mutant, in particular, Pax21Neu, harbors a mutation that is identical to the most commonly occurring PAX2 mutation in humans. Patients with RCS show significant phenotypic variation, even among those with the same mutation. The majority of patients with RCS have optic nerve colobomas and/or related developmental defects affecting the posterior globe. These defects range in severity from bilateral optic nerve colobomas to optic disc dysplasia involving the optic nerve head. PAX2 expression is found to be highest in cells that actively divide during kidney development and in some renal tumors and cystic kidney tissue. PAX2 expression is strongly associated with proliferating cells and following nephrotoxic kidney damage, PAX2 expression is also associated with regenerating kidney cells.