Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2
Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2
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DOI：
10.1016/j.ajhg.2008.12.009
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发表时间：
2009-01-09
影响因子：
9.8
通讯作者：
Warman, Matthew L.
中科院分区：
文献类型：
--
作者：
Neilson, Derek E.;Adams, Mark D.;Warman, Matthew L.
急性坏死性脑病（ANE）是一种快速进行性脑病，可发生在普通病毒感染（如流感和副流感）后的健康儿童中。大多数ANE是散发性和非复发性的（孤立的ANE）。然而，我们确定了一个7 Mb的间隔含有一个易感基因座（ANE 1）在一个家庭分离作为一个不完全的外显，常染色体显性性状的复发ANE。我们现在报告，所有受影响的个人和专性携带者在这个家庭是杂合的错义突变（c.1880C -> T，p.Thr585Met）的基因编码的核孔蛋白Ran结合蛋白2（RANBP 2）。为了确定这种突变是否是易感等位基因，我们筛选了对照组和其他与索引家族无关的ANE患者。15例家族性或复发性ANE患者中有9例有相同的突变。它在两个家庭中重新出现，并在其他几个家庭中独立出现。另外两名家族性ANE患者有不同的RANBP 2错义突变，改变了保守残基。在19例孤立性ANE患者或未受影响的对照组中未发现三种RANBP 2错义突变。我们的结论是RANBP 2的错义突变是家族性和复发性ANE病例的易感等位基因。
Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C -> T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense Mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.