Open AccessGenetic Basis of Type IV Collagen Disorders of the Kidney
Author(s) -
Catherine Quinlan,
Michelle N. Rheault
Publication year - 2021
Publication title -
clinical journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.755
H-Index - 151
eISSN - 1555-905X
pISSN - 1555-9041
DOI - 10.2215/cjn.19171220
Subject(s) - alport syndrome , gene isoform , basement membrane , glomerular basement membrane , type iv collagen , phenotype , kidney , renal function , medicine , extracellular matrix , endocrinology , microbiology and biotechnology , pathology , glomerulonephritis , genetics , biology , gene , laminin
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 α 3(IV), α 4(IV), and α 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.