Alport Syndrome: From Bedside to Genome to Bedside

Clifford Kashtan, Alfred F. Michael

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Alport syndrome is a genetic disorder of basement membranes manifested clinically by a progressive nephropathy and, in many families, sensorineural hearing loss and ocular lesions. During the 1980s evidence was amassed indicating type IV (basement membrane) collagen as the defective protein in Alport syndrome. This hypothesis was confirmed in 1990 by the cloning of the X-chromosomal gene COL4A5, which encodes the α5 chain of type IV collagen, and the discovery of mutations in this gene in many Alport kindreds. The results of recent studies suggest that the α5(IV) chain forms a distinct collagenous network with the α3 and α4 chains of type IV collagen and that mutations in α5(IV) may prevent the normal incorporation of α3(IV) and α4(IV) into basement membranes. Renal biopsy remains an important modality for making the diagnosis of Alport syndrome, but may eventually be replaced by molecular genetic techniques. Posttransplant anti-glomerular basement membrane nephritis occurs rarely in Alport patients and may be restricted to a subgroup with particular COL4A5 mutations. It is not clear why COL4A5 mutations result in glomerulosclerosis and renal failure, or whether this process may be slowed through dietary or pharmacologic intervention.

Original languageEnglish (US)
Pages (from-to)627-640
Number of pages14
JournalAmerican Journal of Kidney Diseases
Issue number5
StatePublished - 1993


  • Alport syndrome
  • basement membranes
  • type IV collagen


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