Genetic and clinical heterogeneity in eIF2B-related disorder
Genetic and clinical heterogeneity in eIF2B-related disorder
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DOI：
10.1177/0883073807308705
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发表时间：
2008-02-01
影响因子：
1.9
通讯作者：
Vanderver, Adeline
中科院分区：
文献类型：
--
作者：
Maletkovic, Jelena;Schiffmann, Raphael;Vanderver, Adeline
真核起始因子2B（eIF 2B）相关疾病是具有可变临床表型（包括消失型白色疾病和卵巢脑白质营养不良）和同样异质的基因型的遗传性白色疾病。我们报告了9个新的突变在EIF2B基因在我们的受试者群体，增加了已知的突变的数量超过120。使用同源建模，我们分析了新的突变对eIF2B蛋白的5个亚基的影响。尽管在EIF 2B基因的CpG二核苷酸处发现了复发性突变，但私密或低频突变的高发生率增加了对这种疾病进行快速遗传确认的挑战，并限制了EIF 2B筛查在未诊断的脑白质营养不良病例中的应用。
Eukaryotic initiation factor 2B (eIF2B)-related disorders are heritable white matter disorders with a variable clinical phenotype (including vanishing white matter disease and ovarioleukodystrophy) and an equally heterogeneous genotype. We report 9 novel mutations in the EIF2B genes in our subject population, increasing the number of known mutations to more than 120. Using homology modeling, we have analyzed the impact of novel mutations on the 5 subunits of the eIF2B protein. Although recurrent mutations have been found at CpG dinucleotides in the EIF2B genes, the high incidence of private or low frequency mutations increases the challenge of providing rapid genetic confirmation of this disorder, and limits the application of EIF2B screening in cases of undiagnosed leukodystrophy.