Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane

Matrix Biol. 2018 Oct;71-72:250-261. doi: 10.1016/j.matbio.2018.04.008. Epub 2018 Apr 16.

Abstract

The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / metabolism
  • Abnormalities, Multiple / pathology
  • Collagen Type IV / chemistry
  • Collagen Type IV / genetics
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / metabolism
  • Eye Abnormalities / pathology
  • Glomerular Basement Membrane / metabolism
  • Glomerular Basement Membrane / pathology*
  • Humans
  • Laminin / chemistry
  • Laminin / genetics
  • Mutation
  • Myasthenic Syndromes, Congenital
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / metabolism
  • Nephritis, Hereditary / pathology
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / metabolism
  • Nephrotic Syndrome / pathology
  • Pupil Disorders / genetics*
  • Pupil Disorders / metabolism
  • Pupil Disorders / pathology

Substances

  • Collagen Type IV
  • Laminin

Supplementary concepts

  • Pierson syndrome