Published on Sat Jul 10 2021

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

Judy Savige, Philip Harraka

Massively Parallel Sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3 - COL4A5) in up to 30 % of individuals with focal and segmental glomerulosclerosis (FSGS) 10 % of those with kidney failure of unknown cause

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Abstract

Massively Parallel Sequencing identifies pathogenic variants in the genes affected in Alport syndrome (COL4A3 - COL4A5) in up to 30 % of individuals with focal and segmental glomerulosclerosis (FSGS), 10 % of those with kidney failure of unknown cause and 20 % with familial IgA glomerulonephritis. FSGS associated with COL4A3 - COL4A5 variants is usually present by kidney failure onset 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 and not pathogenic. However, since some of these variants occur more often than they should by chance, some may be pathogenic. COL4A3 - COL4A5 variants are sometimes also found in cystic kidney diseases after autosomal dominant polycystic kidney disease (ADPKD) has been excluded. COL4A3 - COL4A5 variants should be suspected in individuals with FSGS, kidney failure of unknown cause, or familial IgA glomerulonephritis, especially where there is persistent haematuria, and a family history of haematuria or kidney failure.