大规模平行测序鉴定了多达30％的局灶性和节段性肾小球硬化（FSGS）个体中受Alport综合征（COL4A3-COL4A5）影响的基因中的致病变异，10%的不明原因肾衰竭患者,20％患有家族性免疫球蛋白A（IgA）肾小球肾炎。与COL4A3-COL4A5变体相关的FSGS通常在肾衰竭发作时存在，并且可能由于异常的肾小球膜导致足细胞损失和继发性超滤而发展。COL4A3-COL4A5变体与肾衰竭或IgA肾小球肾炎的关联可能是巧合。然而,在这些情况下，致病变异的发生频率超过了偶然的机会，这表明这些变异是致病的。COL4A3-COL4A5变体也在常染色体显性多囊肾病被排除后的囊性肾病中发现。COL4A3-COL4A5变体应被怀疑为FSGS患者，不明原因的肾衰竭，或家族性IgA肾小球肾炎，尤其是有持续性血尿和血尿或肾衰竭家族史的地方。
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 than they should by chance, which suggests that the variants are disease-causing.
COL4A3-COL4A5 variants are also found in cystic kidney diseases after autosomal dominant polycystic kidney disease 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 hematuria and a family history of hematuria or kidney failure.
