title: COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy.
abstract: Type IV collagen α1 and α2 chains form heterotrimers that constitute an essential component of basement membranes. Mutations in COL4A1, encoding the α1 chain, cause a multisystem disease with prominent cerebrovascular manifestations, including porencephaly, bleeding-prone cerebral small vessel disease, and intracranial aneurysms. Mutations in COL4A2 have only been reported in a few porencephaly families so far. Herein, we report on a young adult patient with recurrent intracerebral hemorrhage, leukoencephalopathy, intracranial aneurysms, nephropathy, and myopathy associated with a novel COL4A2 mutation. We extensively investigated a 29-year-old male patient with recurrent deep intracerebral hemorrhages causing mild motor and sensory hemisyndromes. Brain MRI showed deep intracerebral hemorrhages of different age, diffuse leukoencephalopathy, multiple cerebral microbleeds and small aneurysms of the carotid siphon bilaterally. Laboratory work-up revealed significant microscopic hematuria and elevation of creatine-kinase. Genetic testing found a de novo glycine mutation within the COL4A2 triple helical domain. The presented case completes the spectrum of cerebral and systemic manifestations of COL4A2 mutations that appears to be very similar to that in COL4A1 mutations. Therefore, we emphasize the importance of screening both COL4A1 and COL4A2 in patients showing recurrent intracerebral hemorrhage of unknown etiology, particularly if associated with leukoencephalopathy.
authors.affiliation: Department of Neurology, Semmelweis University, Balassa u. 6, Budapest, 1083, Hungary, gundazez@hotmail.com.
authors.forename: Bence
authors.initials: B
authors.lastname: Gunda
authors.forename: Manuele
authors.initials: M
authors.lastname: Mine
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovács
authors.forename: Csilla
authors.initials: C
authors.lastname: Hornyák
authors.forename: Dániel
authors.initials: D
authors.lastname: Bereczki
authors.forename: György
authors.initials: G
authors.lastname: Várallyay
authors.forename: Gábor
authors.initials: G
authors.lastname: Rudas
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrezet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Tournier-Lasserve
mesh_terms: D000328:Adult; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D005820:Genetic Testing; D005998:Glycine / Q000235:genetics; D006801:Humans; D002532:Intracranial Aneurysm / Q000175:diagnosis / Q000235:genetics; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012008:Recurrence
chemical_list: C502625:COL4A2 protein, human; D024141:Collagen Type IV; D005998:Glycine