Neuropathology and Genetics of Cerebroretinal Vasculopathies
Neuropathology and Genetics of Cerebroretinal Vasculopathies
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DOI：
10.1111/bpa.12178
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发表时间：
2014-09-01
期刊：
影响因子：
6.4
通讯作者：
Vinters, Harry V.
中科院分区：
文献类型：
--
作者：
Kolar, Grant R.;Kothari, Parul H.;Vinters, Harry V.
脑视网膜血管病（CRV）和相关疾病遗传性内皮病伴视网膜病变、神经病变和卒中（HERNS）、遗传性血管性视网膜病变（HVR）和遗传性全身性血管病（HSA）[随后合并为视网膜血管病和脑白质营养不良（RVCL）]是早期至中年发病的毁灭性常染色体显性疾病，表现为神经系统和眼科表现的核心星座。这个疾病家族通过靶向基因核心区域的特定突变而联系在一起。三引物核酸外切酶-1（TREX 1）（染色体3p21.1-p21.3上的主要哺乳动物3 - 5 DNA核酸外切酶）羧基末端的移码突变导致全身性血管病变，其病程约为5年，导致继发于进行性神经功能衰退的死亡，有时在HERNS中病程更长。神经病理学特征包括纤维素样血管坏死或增厚的玻璃样血管，伴有白色物质缺血、坏死和常见的显著营养不良性钙化。血管壁的超微结构研究经常显示不寻常的多层基底膜。
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.