Inherited Diseases of the Glomerular Basement Membrane

Abstract

The glomerular basement membrane (GBM) is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen along with laminin isoforms, nidogens, and the heparan sulfate proteoglycans: perlecan, agrin, and type XVIII collagen. Specific isoforms of type IV collagen, the α3(IV), α4(IV), and α5(IV) isoforms, assemble into trimers that are required for normal GBM function. Mutations in these type IV collagen isoforms cause dysfunction of the GBM that varies depending on genotype and sex and is called Alport syndrome. Classic Alport syndrome is characterized by glomerular hematuria with variably progressive chronic kidney disease, sensorineural hearing loss, and ocular findings. Mutations in laminin β2 cause Pierson syndrome manifesting as congenital nephrotic syndrome. Additional disorders with abnormal findings in the GBM on kidney biopsy include nail-patella syndrome and MYH9-related disorders.