Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease
Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease
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DOI：
10.1373/clinchem.2005.055053
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发表时间：
2005-11-01
影响因子：
9.3
通讯作者：
Hathout, Y
中科院分区：
文献类型：
--
作者：
Vanderver, A;Schiffmann, R;Hathout, Y
背景：用于诊断儿童期共济失调和中枢神经系统髓鞘形成不足（CACH）/消失性白质病（VWM）的生物标志物将具有临床实用性和病理生理学意义。方法：我们使用二维凝胶、电泳/错过光谱法来比较突变确认的 CACH/VWM 患者与未受影响的对照患者的脑脊液蛋白质组。我们通过凝胶内消化、基质辅助激光解吸/电离飞行时间串联质谱和纳喷雾傅里叶变换质谱对选定的斑点进行了表征。结果：在 CACH/VWM 组 (n = 7) 的 CSF 样本中检测到特定的转铁蛋白斑点模式，将其与对照组 (n = 23) 区分开来，并揭示 CACH/VWM 患者缺乏通常存在于体内的去唾液酸形式的转铁蛋白。健康的脑脊液。通过凝胶内消化从分离的转铁蛋白点确定糖肽结构。提取出来，发现是一致的。结论：CACH/VWM 患者脑脊液中转铁蛋白异构体异常显得独特，是一种潜在的临床诊断生物标志物。这种疾病的快速、有效的诊断将对探索这种疾病的管理和治疗新策略的临床研究产生重大影响。 (c) 2005 年美国临床化学协会。
Background: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would hive clinical utility and pathophysiologic significance.Methods: We used 2-dimensional gel, electrophoresis/ miss spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/ VWM with that of unaffected controls. We characterised selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry.Results: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and. extraction, was found to be consistent. with earlier reports.Conclusion: The transferrin isoform abnormality in the cerebrospinal fluid of Patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would hive a significant impact on clinical studies exploring,new strategies for the management and treatment of this disease. (c) 2005 American Association for Clinical Chemistry.