Neuropathology and Genetics of Cerebroretinal Vasculopathies. (September 2014)

• Record Type: Journal Article
• Authors: Kolar, Grant R.; Kothari, Parul H.; Khanlou, Negar; Jen, Joanna C.; Schmidt, Robert E.; Vinters, Harry V.
• Is Part Of: Brain pathology. Volume 24:Number 5(2014:Sep.)
• Page Start: 510
• Page End: 518
• Publication Date: 2014-09
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12178
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>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 <underline>t</underline>hree <underline>p</underline>rime <underline>e</underline>xonuclease‐<underline>1</underline> (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.</p> </abstract>