Research Paper: 2005 Gould

Date Published : 05/20/2005

Summary: Mutations in Col4a1 Cause Perinatal Cerebral Hemorrhage and Porencephaly

Abstract: 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 È18% of survivors had porencephaly. We show that vascular defects are caused by a semidominant mutation in the procollagen type IV a 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.

Mutations in Col4a1 Cause Perinatal Cerebral Hemorrhage and Porencephaly