PAX2

More than 40 variants (also known as mutations) in the PAX2 gene have been found to cause renal coloboma syndrome. Most variants are specific to each affected family; however, one variant has been found in multiple affected individuals. This variant inserts one DNA building block (nucleotide) into the PAX2 gene (written as 619insG). Most variants occur in the region of the protein that attaches to DNA, impairing its function as a transcription factor. A lack of functional PAX2 protein disrupts the formation of certain tissues (particularly the kidneys and eyes) during embryonic development, causing the signs and symptoms of renal coloboma syndrome.

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More than 20 variants in the PAX2 gene have been found in people with abnormalities of the kidneys and other structures of the urinary system but without the eye problems of renal coloboma syndrome (described above). The urinary system abnormalities vary in severity and are grouped together as congenital anomalies of kidney and urinary tract (CAKUT). The most severe CAKUT abnormalities can cause kidney damage and life-threatening kidney failure.

The effects of CAKUT-associated PAX2 gene variants are not fully understood, but it is likely that they impair the function of the PAX2 protein, disrupting formation of the kidneys and urinary system during embryonic development. It is unclear why only structures of the urinary system are affected in these individuals.

PAX2 gene variants are also found in individuals with abnormalities of the optic nerve, which carries visual information from the eyes to the brain. These individuals do not have the kidney anomalies associated with renal coloboma syndrome (described above). As in renal coloboma syndrome, the PAX2 gene variants associated with eye abnormalities likely disrupt regulation of genes that help direct normal eye development. Researchers are working to understand why variants in this gene can affect different organ systems in different people.