Mutations in Col4a 1 Cause Perinatal Cerebral Hemorrhage and Porencephaly.

Porencephaly is a rare neurological disease, typically manifest ininfants, which is characterized by the existence of degenerativecavities in the brain. To investigate the molecular pathogenesis ofporencephaly, we studied a mouse mutant that develops porencephalysecondary to focal disruptions of vascular basement membranes. Half ofthe mutant mice died with cerebral hemorrhage within a day of birth, and~18% of survivors had porencephaly. We show that vascular defects arecaused by a semidominant mutation in the procollagen type IV α 1gene (Col4a1) in mice, which inhibits the secretion of mutant and normaltype IV collagen. We also show that COL4A1 mutations segregate withporencephaly in human families. Because not all mutant mice developporencephaly, we propose that Col4a1 mutations conspire withenvironmental trauma in causing the disease. [ABSTRACT FROM AUTHOR]