C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease.
C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease.
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DOI：
10.1038/s41598-017-06604-2
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发表时间：
2017-07-21
影响因子：
4.6
通讯作者：
Rolfs A
中科院分区：
文献类型：
--
作者：
Cozma C;Iurașcu MI;Eichler S;Hovakimyan M;Brandau O;Zielke S;Böttcher T;Giese AK;Lukas J;Rolfs A
法伯病（FD）是一种罕见的常染色体隐性遗传病，由酸性神经酰胺酶基因（ASAH 1）突变引起。低神经酰胺酶活性导致脂肪物质，主要是神经酰胺的积累。临床上的标志性症状是关节周围结节、脂肪肉芽肿、关节肿胀和疼痛以及声音嘶哑。FD表型是异质性的，从轻度到非常严重的病例，患者不能存活超过他们的第一年。FD的诊断方面是欠发达，由于罕见的疾病。在本研究中，在法伯病患者（n = 10）、携带者（n = 11）和对照个体（n = 192）中进行神经酰胺和相关分子的筛查。这项研究有最高数量的法伯患者和运营商报告目前。液相色谱多反应质谱（LC/MRM-MS）研究表明，神经酰胺C26：0，尤其是其亚型1是FD的高度敏感和特异性生物标志物（p < 0.0001）。新的生物标志物可以直接在干血斑提取物中测定，样品消耗量低。这允许容易的样品制备、高再现性和在高通量筛选中的使用。
Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease. In the present study, the screening for ceramides and related molecules was performed in Farber affected patients (n = 10), carriers (n = 11) and control individuals (n = 192). This study has the highest number of enrolled Farber patients and carriers reported to present. Liquid chromatography multiple reaction mass spectrometry (LC/MRM-MS) studies revealed that the ceramide C26:0 and especially its isoform 1 is a highly sensitive and specific biomarker for FD (p < 0.0001). The new biomarker can be determined directly in the dried blood spot extracts with low sample consumption. This allows for easy sample preparation, high reproducibility and use in high throughput screenings.
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DOI：
10.1007/8904_2013_246
发表时间：
2014-01-01
期刊：
JIMD REPORTS, VOL 12
影响因子：
--
作者：
Ferreira, Natalia Santos;Goldschmidt-Arzi, Michal;Futerman, Anthony H.
通讯作者：
Futerman, Anthony H.
影响因子：
9.3
作者：
De Jesus, Victor R.;Zhang, X. Kate;Hannon, W. Harry
通讯作者：
Hannon, W. Harry
影响因子：
11.1
作者：
Alayoubi, Abdulfatah M.;Wang, James C. M.;Medin, Jeffrey A.
通讯作者：
Medin, Jeffrey A.
影响因子：
3.9
作者：
Bär, J;Linke, T;Sandhoff, K
通讯作者：
Sandhoff, K
影响因子：
3.5
作者：
Hammad SM;Baker NL;El Abiad JM;Spassieva SD;Pierce JS;Rembiesa B;Bielawski J;Lopes-Virella MF;Klein RL;DCCT/EDIC Group of Investigators
通讯作者：
DCCT/EDIC Group of Investigators