title: Neuropathology and genetics of cerebroretinal vasculopathies.
abstract: Cerebroretinal vasculopathy (CRV) and the related diseases hereditary endotheliopathy with retinopathy, neuropathy, and stroke (HERNS), hereditary vascular retinopathy (HVR) and hereditary systemic angiopathy (HSA) [subsequently combined as retinovasculopathy and cerebral leukodystrophy (RVCL)] are devastating autosomal-dominant disorders of early to middle-age onset presenting with a core constellation of neurologic and ophthalmologic findings. This family of diseases is linked by specific mutations targeting a core region of a gene. Frameshift mutations in the carboxyl-terminus of three prime exonuclease-1 (TREX1), the major mammalian 3' to 5' DNA exonuclease on chromosome 3p21.1-p21.3, result in a systemic vasculopathy that follows an approximately 5-year course leading to death secondary to progressive neurologic decline, with sometimes a more protracted course in HERNS. Neuropathological features include a fibrinoid vascular necrosis or thickened hyalinized vessels associated with white matter ischemia, necrosis and often striking dystrophic calcifications. Ultrastructural studies of the vessel walls often demonstrate unusual multilaminated basement membranes.
authors.affiliation: Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Kolar
authors.forename: Parul H
authors.initials: PH
authors.lastname: Kothari
authors.forename: Negar
authors.initials: N
authors.lastname: Khanlou
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Jen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
mesh_terms: D001921:Brain / Q000098:blood supply / Q000648:ultrastructure; D005090:Exodeoxyribonucleases / Q000235:genetics*; D016368:Frameshift Mutation; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000648:ultrastructure; D010750:Phosphoproteins / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology*; D014652:Vascular Diseases / Q000235:genetics* / Q000473:pathology*
chemical_list: D010750:Phosphoproteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1
keywords: CRV; HERNS; and stroke; cerebral microvascular disease; hereditary endotheliopathy with retinopathy; hereditary vascular retinopathy; nephropathy; ocular microvascular disease