title: A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly.
abstract: We describe a three generation family with recurrent strokes and cataracts. The index case, a 14 year old boy presented with stroke at the age of 14 years and again 6 months later. His mother had long standing episodic headaches diagnosed as migraine. Grandmother was initially diagnosed with multiple sclerosis and had recurrent strokes at age 18 years and 49 years. MRI scanning showed a diffuse leukoencephalopathy with microhaemorrhages in all three individuals. All of the family members had cataracts but did not have retinal arterial changes. Sequence analysis of COL4A1 revealed the heterozygous missense mutation c.2263G-->A in exon 30, responsible for a glycine-to-arginine substitution (p.Gly755Arg) in both the index case and mother. Grandmother died at the age of 73 years and DNA analysis was not possible. Mutation in COL4A1 should be considered in families with a history of autosomal dominant cerebral vasculopathy, even in the absence of porencephaly.
authors.affiliation: Department of Paediatric Neurology, Bristol Royal Hospital for Children, United Kingdom.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Shah
authors.forename: Yadlapalli
authors.initials: Y
authors.lastname: Kumar
authors.forename: Brendan
authors.initials: B
authors.lastname: McLean
authors.forename: Amanda
authors.initials: A
authors.lastname: Churchill
authors.forename: Neil
authors.initials: N
authors.lastname: Stoodley
authors.forename: Julia
authors.initials: J
authors.lastname: Rankin
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rizzu
authors.forename: Marjo
authors.initials: M
authors.lastname: van der Knaap
authors.forename: Philip
authors.initials: P
authors.lastname: Jardine
mesh_terms: D000293:Adolescent; D000328:Adult; D002386:Cataract / Q000175:diagnosis / Q000235:genetics*; D003094:Collagen / Q000235:genetics*; D015140:Dementia, Vascular / Q000175:diagnosis / Q000453:epidemiology*; D005091:Exons / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis / Q000453:epidemiology; D009103:Multiple Sclerosis / Q000453:epidemiology; D020125:Mutation, Missense / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C054447:COL14A1 protein, human; D006023:Glycoproteins; D003094:Collagen