Role of COL4A1 in small-vessel disease and hemorrhagic stroke

N Engl J Med. 2006 Apr 6;354(14):1489-96. doi: 10.1056/NEJMoa053727.


Small-vessel diseases of the brain underlie 20 to 30 percent of ischemic strokes and a larger proportion of intracerebral hemorrhages. In this report, we show that a mutation in the mouse Col4a1 gene, encoding procollagen type IV alpha1, predisposes both newborn and adult mice to intracerebral hemorrhage. Surgical delivery of mutant mice alleviated birth-associated trauma and hemorrhage. We identified a COL4A1 mutation in a human family with small-vessel disease. We concluded that mutation of COL4A1 may cause a spectrum of cerebrovascular phenotypes and that persons with COL4A1 mutations may be predisposed to hemorrhage, especially after environmental stress.

Publication types

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

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / pathology
  • Cerebral Hemorrhage / etiology
  • Cerebral Hemorrhage / genetics*
  • Collagen Type IV / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Glomerular Basement Membrane / abnormalities
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL / genetics
  • Mice, Mutant Strains
  • Microcirculation
  • Mutation*
  • Pedigree
  • Renal Artery / abnormalities
  • Retinal Artery / abnormalities
  • Risk Factors
  • Stress, Physiological / complications
  • Stroke / etiology
  • Stroke / genetics


  • Collagen Type IV