Novel diagnostic approach to citrin deficiency: Analysis of citrin protein in lymphocytes
Novel diagnostic approach to citrin deficiency: Analysis of citrin protein in lymphocytes
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DOI：
10.1016/j.ymgme.2006.09.009
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发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Okano, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Tokuhara, Daisuke;Iijima, Mikio;Okano, Yoshiyuki
柑橘缺乏症会导致两种临床特征：即柠檬酸缺乏引起的新生儿肝内胆汁淤积症（NICCD）和成人发病的11型瓜氨酸血症。高瓜氨酸血症是最典型的特征，而也存在非瓜氨酸血症个体。柑橘缺乏症的诊断是通过基因分析进行的，尽管在约 15% 的病例中未检测到 12 种已知的等位基因突变。因此，我们的目的是检查从外周血中分离的淋巴细胞中的柑橘蛋白，作为替代诊断方法。我们检查了 38 名患有胆汁淤积性肝功能障碍的儿童、8 名杂合子和 1 名健康个体。通过蛋白质印迹法评估所有受试者的柑橘蛋白，并通过基因分析评估 12 种已知突变。 38 名患有胆汁淤积性肝功能障碍的儿童中，有 15 名检测到了 Citrin 蛋白。其中 14 名患者的两个等位基因中 12 种已知突变均呈阴性，而一名患者的一个等位基因中存在已知突变。 38 名患者中有 23 名缺乏 Citrin 蛋白。在这 23 名患者中，基因分析诊断出 19 名患者缺乏 citrin，而 2 名患者后来被发现患有新突变的 NICCD。在其余 2 名表现出 NICCD 临床特征的患者中，在一个等位基因中检测到已知突变，但在另一个等位基因中未发现突变。在 8 个杂合子和健康个体中也检测到了 Citrin 蛋白。我们发现柠檬酸缺乏症患者的淋巴细胞中缺乏柠檬酸。即使对于没有已知突变或高瓜氨酸血症的患者，柠檬酸分析也可用于诊断柠檬酸缺乏症。 (c) 2006 Elsevier Inc. 保留所有权利。
Citrin deficiency induces two clinical features; namely neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 11 citrullinemia. Hypercitrullinemia is the most characteristic feature, whereas there are non-citrullinemic individuals. Diagnosis of citrin deficiency is performed by genetic analysis, although the 12 known mutations in the alleles are not detected in about 15% of cases. Thus, we aimed to examine citrin protein in lymphocytes isolated from peripheral blood as an alternative diagnostic method. We examined 38 children having an episode of cholestatic liver dysfunction, 8 heterozygotes, and I I healthy individuals. All subjects were evaluated for citrin protein by Western blotting and for the 12 known mutations by gene analysis. Citrin protein was detected in 15 of 38 children with cholestatic liver dysfunction. Fourteen of them were negative for 12 known mutations in both alleles, whereas one patient was found to have a known mutation in one allele. Citrin protein was absent in 23 of the 38 patients. Among these 23, gene analysis diagnosed citrin deficiency in 19, whereas 2 patients were later revealed to be NICCD with novel mutations. In the remaining 2 patients, who exhibit the clinical features of NICCD, a known mutation was detected in one allele but no mutation was identified in another allele. Citrin protein was also detected in the 8 heterozygotes and I I healthy individuals. We disclosed that citrin was deficient in lymphocytes among patients with citrin deficiency. Analysis of citrin is useful to diagnose citrin deficiency even in patients without known mutations or hypercitrullinemia. (c) 2006 Elsevier Inc. All rights reserved.