Hereditary abnormalities of renal basement membranes.
The glomerular and tubular basement membranes are the principal barriers to filtration and re-absorption of water and molecules in the nephron. They are composed primarily of type IV collagen, laminin, fibronectin, sulphated proteoglycans and collagen type I. Three common inherited diseases are associated with abnormalities of basement membrane proteins: Alport's syndrome, thin basement membrane disease (TBMD) and adult polycystic kidney disease. In this review we describe the application of molecular biological techniques to the study of these conditions. Classic Alport's syndrome is an X-linked disorder with a lamellated glomerular basement membrane (GBM) which typically results in renal failure in males. Studies with sera from patients with Goodpasture's syndrome, or monoclonal antibodies specific for the Goodpasture antigen, show that the Goodpasture antigen is absent or masked in the kidneys of individuals with Alport's syndrome. There is some evidence to suggest that the Goodpasture antigen is best represented by the non-collagenous domain of the alpha 3 chain of type IV collagen, but that other non-collagenous regions may also contribute to the antigen. It is through these non-collagenous regions that the type IV collagen chains form the typical network, and the abnormality in Alport's syndrome interferes with this network formation. However, we have recently demonstrated that the gene for the non-collagenous domain of the alpha 3 collagen chain is present in individuals with Alport's syndrome. Furthermore, other groups have shown a defect in a novel type IV collagen chain, the alpha 5 chain, in 3 unrelated cases of Alport's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Haematology, Repatriation General Hospital, Heidelberg, Victoria.
J
J
Savige
D001485:Basement Membrane / Q000737:chemistry / Q000648:ultrastructure; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002885:Chromosomes, Human, Pair 16; D003094:Collagen / Q000032:analysis / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics; D015342:DNA Probes; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure*; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D015342:DNA Probes; D003094:Collagen; D004247:DNA