Towards a New Diagnostic Standard for Niemann-Pick C Disease.
Towards a New Diagnostic Standard for Niemann-Pick C Disease.
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DOI：
10.1016/j.ebiom.2016.01.004
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发表时间：
2016-02
期刊：
影响因子：
11.1
通讯作者：
Ory DS
中科院分区：
文献类型：
--
作者：
Jiang X;Ory DS
尼曼-皮克C(NPC)病是一种罕见的神经退行性、溶酶体胆固醇储存障碍。由于疾病的异质性、非特异性的早期内脏和神经症状以及缺乏快速可靠的诊断方法，该病的诊断往往被延误。直到最近，鼻咽癌疾病的主要诊断试验是从皮肤活检获得的培养成纤维细胞中未酯化胆固醇的非酯化胆固醇染色。尽管Filipin分析对诊断“经典”疾病是敏感的，但它不能在具有代表N1/3鼻咽癌病例的“变异”表型的成纤维细胞中提供确切的诊断(Stampfer等人，2013年)。此外，这种测试是侵入性的，只在专门的中心进行，费用昂贵(3000美元)，通常需要大约3个月的周转时间，所有这些都阻碍了广泛的临床部署。基因分析，包括NPC1和NPC2基因的测序，是一种重要的诊断工具，尽管出于成本考虑，它通常被用作确证测试而不是筛查测试。此外，常规基因测序只在85%的病例中检测到两个等位基因的突变，并被NPC1的高度多态性质(N400已知突变)所混淆，这使得对新突变的解释具有挑战性(Stampfer等人，2013年)。在过去的几年里，生物标记物的发现工作导致了几个有前途的鼻咽癌疾病生物标记物的识别。其中一种标志物，Cholestane-3β，5α，6β-Triol(“三醇”)，是一种胆固醇氧化产物，已成为鼻咽癌疾病的敏感诊断(Porter等人，2010年)。该生物标志物在鼻咽癌快速诊断中的应用已在多个中心和不同的平台上得到验证(Boenzi等人，2014年；Klinke等人，2015年；Pajares等人，2015年；Polo等人，2015年；酱等人，2011年)。在本期的《生态医学》杂志中，
Niemann–Pick C (NPC) disease is rare, neurodegenerative, lysosomal cholesterol storage disorder. Diagnosis of the disease is often delayed due to disease heterogeneity, non-specific early visceral and neurological symptoms, and lack of a rapid and reliable diagnostic assay. As a result, the disease progresses and opportunities to intervene tragically are lost.Until recently, the principal diagnostic test for NPC disease was filipin staining of unesterified cholesterol in cultured fibroblasts obtained from a skin biopsy. While the filipin assay is sensitive for diagnosis of “classical” disease, it is unable to provide a firm diagnosis in fibroblasts with “variant” phenotypes that represent N1/3 of NPC cases (Stampfer et al., 2013). Moreover, the test is invasive, performed only at specialized centers, is costly (3000 USD), and generally entails~ 3 month turnaround time, all of which are disincentives for broad clinical deployment. Genetic analysis, involving sequencing of the NPC1 and NPC2 genes, is an important diagnostic tool, though, due to cost considerations, it is generally applied as a confirmatory rather than screening test. Furthermore, routine gene sequencing detects mutations on both alleles in only 85% cases and is confounded by the highly polymorphic nature of NPC1 (N400 known mutations), which makes interpretation of new mutations challenging (Stampfer et al., 2013). Over the past several years, biomarker discovery efforts have led to identification of several promising NPC disease biomarkers. One of these markers, cholestane-3β, 5α, 6β-triol (“triol”), which is a cholesterol oxidation product, has emerged as a sensitive diagnostic for NPC disease (Porter et al., 2010). The application of this biomarker to rapid diagnosis of NPC has been demonstrated at multiple centers and on diverse platforms (Boenzi et al., 2014; Klinke et al., 2015; Pajares et al., 2015; Polo et al., 2015; Jiang et al., 2011). In this issue of EBioMedicine,