The clinical spectrum of type IV collagen mutations

Hum Mutat. 1997;9(6):477-99. doi: 10.1002/(SICI)1098-1004(1997)9:6<477::AID-HUMU1>3.0.CO;2-#.


Clinical manifestations of type IV collagen mutations can vary from the severe, clinically and genetically heterogeneous renal disorder, Alport syndrome, to autosomal dominant familial benign hematuria. The predominant form of Alport syndrome is X-linked; more than 160 different mutations have yet been identified in the type IV collagen alpha 5 chain (COL4A5) gene, located at Xq22-24 head to head to the COL4A6 gene. The autosomal recessive form of Alport syndrome is caused by mutations in the COL4A3 and COL4A4 genes, located at 2q35-37. Recently, the first mutation in the COL4A4 gene was identified in familial benign hematuria. This paper presents an overview of type IV collagen mutations, including eight novel COL4A5 mutations from our own group in patients with Alport syndrome. The spectrum of mutations is broad and provides insight into the clinical heterogeneity of Alport syndrome with respect to age at renal failure and accompanying features such as deafness, leiomyomatosis, and anti-GBM nephritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Child
  • Codon, Terminator / genetics
  • Collagen / chemistry
  • Collagen / genetics*
  • Collagen / physiology
  • Deafness / genetics
  • Gene Expression
  • Gene Rearrangement
  • Genotype
  • Glomerulonephritis / genetics
  • Hematuria / genetics
  • Humans
  • Leiomyomatosis / genetics
  • Molecular Structure
  • Mutation*
  • Nephritis, Hereditary / diagnosis
  • Nephritis, Hereditary / genetics
  • Nephritis, Hereditary / metabolism
  • Phenotype
  • Point Mutation


  • Codon, Terminator
  • Collagen