Role of COL4A1 in small-vessel disease and hemorrhagic stroke.
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.
Gould
Douglas B
DB
Howard Hughes Medical Institute, Bar Harbor, Me, USA.
Phalan
F Campbell
FC
van Mil
Saskia E
SE
Sundberg
John P
JP
Vahedi
Katayoun
K
Massin
Pascale
P
Bousser
Marie Germaine
MG
Heutink
Peter
P
Miner
Jeffrey H
JH
Tournier-Lasserve
Elisabeth
E
John
Simon W M
SW
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D050533:Glomerular Basement Membrane / Q000002:abnormalities; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008817:Mice, Mutant Strains; D008833:Microcirculation; D009154:Mutation; D010375:Pedigree; D012077:Renal Artery / Q000002:abnormalities; D012161:Retinal Artery / Q000002:abnormalities; D012307:Risk Factors; D013312:Stress, Physiological / Q000150:complications; D020521:Stroke / Q000209:etiology / Q000235:genetics
D024141:Collagen Type IV