Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly

Douglas B. Gould, F. Campbell Phalan, Guido J. Breedveld, Saskia E. Van Mil, Richard S. Smith, John C. Schimenti, Umberto Aguglia, Marjo S. Van Der Knaap, Peter Heutink, Simon W.M. John*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 ∼18% of survivors had porencephaly. We show that vascular defects are caused by a semidominant mutation in the procollagen type IV α 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.

Original languageEnglish
Pages (from-to)1167-1171
Number of pages5
Issue number5725
Publication statusPublished - 20 May 2005

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