Genetic Basis of Type IV Collagen Disorders of the Kidney

The glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the alpha 3(IV), alpha 4(IV), and alpha 5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.

Automated summary

The glomerular basement membrane, primarily composed of type IV collagen, plays a vital role in kidney filtration. Specific isoforms of type IV collagen are essential for normal membrane function and mutations can lead to conditions such as Alport syndrome. Patients with mutations affecting type IV collagen exhibit wide variability in phenotype.