Nemesis of neglected neurosarcoidosis.
Nemesis of neglected neurosarcoidosis.
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被忽视的神经结节病的克星。
DOI：
10.1002/acn3.247
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发表时间：
2015
影响因子：
5.3
通讯作者：
Clifford,DavidB
中科院分区：
文献类型：
--
作者：
Clifford,DavidB
神经结节病(NS)是当神经系统发生非干酪性肉芽肿时诊断的，通常与其他器官的类似病理有关。1虽然肺部和皮肤的表现较为常见，但神经系统的表现包括脑膜炎、脑或脊髓实质损害，或颅神经或周围神经损害，是结节病最严重和最难治疗的表现之一。2、3可能是由于NS的诊断困难、表型和临床病程多变，以及其相对罕见的原因，NS几乎没有受到科学的关注。这是一个严重的遗漏，因为NS通常是致残的，有时甚至是致命的。可悲的是，它甚至不是真正罕见的。事实上，最近在一家大型医学中心对多发性硬化症以外的炎症性脑病进行的一项调查发现，NS是第二常见的炎症性脑病，在频率上与视神经脊髓炎相同。4尽管这些令人信服的证据表明了NS的重要性，但目前几乎没有关注它的资助研究项目。本期ACTN中的5篇文章给出了NS将成为21世纪科学的严肃焦点的希望。这篇手稿报道了对染色体15q25的精细定位分析，该分析表明锌指基因ZNF592在NS中存在。在绘制基因组的这一区域时发现了与ZNF592基因变异的显著关联，这一区域怀疑是先前在结节病中进行的全基因组关联研究。主要的关联是从83例非裔美国人NS病例和1645名健康对照人群中确定的。作为验证，在一组更小的患有NS的欧洲裔美国人中发现了该基因的其他变体。这些发现引起了人们对ZNF592的关注，ZNF592似乎与神经系统在大脑中广泛表达有关，并在大脑发育中发挥作用。此外，蛋白质关联表明，该基因可能包括在细胞免疫的控制系统中，这将与诸如NS之类的免疫疾病高度相关。是
Neurosarcoidosis (NS) is diagnosed when noncaseating granulomas develop in the nervous system, often associated with similar pathology in other organs. 1 While lung and skin manifestation are more common, the neurological manifestations including meningitis, parenchymal brain or spinal cord lesions, or cranial or peripheral nerve damage are among the most serious and difficult to treat manifestations of sarcoidosis. 2, 3 Perhaps because of the difficulty diagnosing NS, variable phenotypes and clinical course, as well as its relative rarity, NS has received shockingly little scientific attention. This is a serious omission, since NS is often disabling and sometimes lethal. Sadly, it is not even truly rare. Indeed, a recent survey of inflammatory brain diseases other than multiple sclerosis at a large medical center identified NS as the second most common inflammatory brain disorder, equal in frequency to neuromyelitis optica. 4 Despite this compelling evidence of the importance of NS, there are virtually no current funded research programs focusing on it.Given this background, the report of Lareau et al. 5 in this issue of ACTN gives hope that NS will become a serious focus for 21st century science. The manuscript reports fine mapping analysis of chromosome 15q25 that implicates the zinc finger gene ZNF592 in NS. Significant association to a variant in a gene ZNF592 was found in mapping this region of the genome suspected from a prior genome-wide association study in sarcoidosis. The primary association was defined from a population of 83 African American NS cases compared with 1645 healthy controls. As verification, other variants of this gene were found in an even smaller cohort of European Americans with NS. These findings draw attention to ZNF592 which seems relevant to the nervous system being widely expressed in the brain as well as having a role in cerebral development. Furthermore, protein associations suggest that this gene may be included in control systems for cellular immunity which would be highly relevant to an immune disorder such as NS. Were