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Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly.

Porencephaly is a rare neurological disease, typically manifest in infants, which is characterized by the existence of degenerative cavities in the brain. To investigate the molecular pathogenesis of porencephaly, we studied a mouse mutant that develops porencephaly secondary to focal disruptions of vascular basement membranes. Half of the mutant mice died with cerebral hemorrhage within a day of birth, and approximately 18% of survivors had porencephaly. We show that vascular defects are caused by a semidominant mutation in the procollagen type IV alpha 1 gene (Col4a1) in mice, which inhibits the secretion of mutant and normal type IV collagen. We also show that COL4A1 mutations segregate with porencephaly in human families. Because not all mutant mice develop porencephaly, we propose that Col4a1 mutations conspire with environmental trauma in causing the disease.

Pubmed ID: 15905400


  • Gould DB
  • Phalan FC
  • Breedveld GJ
  • van Mil SE
  • Smith RS
  • Schimenti JC
  • Aguglia U
  • van der Knaap MS
  • Heutink P
  • John SW


Science (New York, N.Y.)

Publication Data

May 20, 2005

Associated Grants

  • Agency: NCI NIH HHS, Id: CA34196
  • Agency: NEI NIH HHS, Id: EY11721

Mesh Terms

  • Alleles
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Animals, Newborn
  • Basement Membrane
  • Brain
  • Brain Diseases
  • Cerebral Hemorrhage
  • Chromosome Mapping
  • Collagen Type IV
  • Endoderm
  • Heterozygote
  • Humans
  • Mice
  • Mutation
  • Protein Structure, Tertiary