Fifteen novel EIF2B1-5 mutations identified in Chinese children with leukoencephalopathy with vanishing white matter and a long term follow-up.
Fifteen novel EIF2B1-5 mutations identified in Chinese children with leukoencephalopathy with vanishing white matter and a long term follow-up.
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十五个新颖的EIF2B1-5突变在中国白血病患者中发现，白质和长期随访。
DOI：
10.1371/journal.pone.0118001
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Zhang H;Dai L;Chen N;Zang L;Leng X;Du L;Wang J;Jiang Y;Zhang F;Wu X;Wu Y
白色消失性脑白质病（Leukoencephalopathy with vanishing white matter，VWM）是一种常见的遗传性儿童白色疾病，由真核细胞翻译起始因子2B（EIF 2B 1 -5）的5个亚基突变引起。在我们的研究中，36例临床诊断的儿童中有34例（94%）通过测序确定具有EIF 2B 1 -5突变。发现15个新突变。在只有一个突变等位基因的患者中未检测到CNVs，并且通过基因测序确定突变阴性。与白人患者相比，EIF 2B 3突变患者的发生率显著更高（32% vs. 4%）。EIF 2B 3基因c.1037T>C（p.Ile346Thr）突变在中国人群中被证实为创始突变，这可能是造成EIF 2B 3基因型种族差异的原因之一。我们对婴儿、幼儿和青少年VWM儿童的平均4.4年随访表明，运动功能迅速恶化。90%的婴儿病例和71.4%的儿童病例出现发作性加重。随访期间死亡10例。Kaplan-Meier曲线显示中位生存期为8.83 ± 1.51年。这是VWM随访研究中最大的儿童样本，有助于更深入地了解自然过程。
Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited childhood white matter disorders, which caused by mutations in each of the five subunits of eukaryotic translation initiation factor 2B (EIF2B1-5). In our study, 34 out of the 36 clinically diagnosed children (94%) were identified to have EIF2B1-5 mutations by sequencing. 15 novel mutations were identified. CNVs were not detected in patients with only one mutant allele and mutation-negative determined by gene sequencing. There is a significantly higher incidence of patients with EIF2B3 mutations compared with Caucasian patients (32% vs. 4%). c.1037T>C (p.Ile346Thr) in EIF2B3 was confirmed to be a founder mutation in Chinese, which probably one of the causes of the genotypic differences between ethnicities. Our average 4.4 years-follow-up on infantile, early childhood and juvenile VWM children suggested a rapid deterioration in motor function. Episodic aggravation was presented in 90% of infantile cases and 71.4% of childhood cases. 10 patients died during the follow-up. The Kaplan-Meier curve showed that the median survival time is 8.83 ± 1.51 years. This is the largest sample of children in a VWM follow-up study, which is helpful for a more depth understanding about the natural course.
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影响因子：
3.7
作者：
Kantor L;Pinchasi D;Mintz M;Hathout Y;Vanderver A;Elroy-Stein O
通讯作者：
Elroy-Stein O
影响因子：
1.9
作者：
Maletkovic, Jelena;Schiffmann, Raphael;Vanderver, Adeline
通讯作者：
Vanderver, Adeline
影响因子：
64.5
作者：
Sonenberg N;Hinnebusch AG
通讯作者：
Hinnebusch AG
影响因子：
2.6
作者：
Horzinski L;Kantor L;Huyghe A;Schiffmann R;Elroy-Stein O;Boespflug-Tanguy O;Fogli A
通讯作者：
Fogli A
影响因子：
3.9
作者：
Fogli, A;Boespflug-Tanguy, O
通讯作者：
Boespflug-Tanguy, O