Pathogenic Variants in the Genes Affected in Alport Syndrome (COL4A3–COL4A5) and Their Association With Other Kidney Conditions: A Review

Abstract

Massively parallel sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3–COL4A5) in as many as 30% of individuals with focal and segmental glomerulosclerosis (FSGS), 10% of those with kidney failure of unknown cause, and 20% with familial immunoglobulin A (IgA) glomerulonephritis. FSGS associated with COL4A3–COL4A5 variants is usually present by the onset of kidney failure and may develop because the abnormal glomerular membranes result in podocyte loss and secondary hyperfiltration. The association of COL4A3–COL4A5 variants with kidney failure or IgA glomerulonephritis may be coincidental. However, pathogenic variants in these conditions occur more often..