Benign familial hematuria due to mutation of the type IV collagen alpha4 gene

J Clin Invest. 1996 Sep 1;98(5):1114-8. doi: 10.1172/JCI118893.


Benign familial hematuria (BFH) is characterized by autosomal dominant inheritance, thinning of the glomerular basement membrane (GBM) and normal renal function. It is frequent in patients with persistent microscopic hematuria, but cannot be clinically differentiated from the initial stages of Alport syndrome, a severe GBM disorder which progresses to renal failure. We present here linkage of benign familial hematuria with the COL4A3 and COL4A4 genes at 2q35-37 (Zmax = 3.58 at theta = 0.0). Subsequently, a glycine to glutamic acid substitution was identified in the collagenous region of the COL4A4 gene. We conclude that type IV collagen defects cause both benign hematuria and Alport syndrome. Furthermore, our data suggest that BFH patients can be carriers of autosomal recessive Alport syndrome.

Publication types

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

MeSH terms

  • Basement Membrane / pathology
  • Chromosomes, Human, Pair 2 / genetics
  • Collagen / genetics*
  • Female
  • Genes, Dominant
  • Genes, Recessive
  • Genetic Linkage
  • Hematuria / epidemiology
  • Hematuria / etiology
  • Hematuria / genetics*
  • Heterozygote
  • Humans
  • Kidney Glomerulus / pathology
  • Male
  • Mutation*
  • Nephritis, Hereditary / epidemiology
  • Nephritis, Hereditary / etiology
  • Nephritis, Hereditary / genetics*
  • Netherlands / epidemiology
  • Pedigree
  • Sequence Analysis, DNA


  • Collagen