Association of RANBP2 with cytokine storm and cellular energy

细胞因子风暴可能在日本公认的急性坏死性脑病（ANE）的病理机制中起重要作用。目前还不清楚ANE是否由单个基因突变（如RANBP 2）引起。我们对RANBP 2的潜在结合蛋白考克斯基因进行了遗传学分析，并对线粒体电子传递系统进行了协同作用。在24例ANE患者中未检测到COX11和COX17的突变。我们在一例ANE患者中发现了COX10基因第3外显子的杂合性氨基酸替换。3例患者携带COX15基因rs2231682的次要等位基因A（MAF <0.01）。我们认为COX的这些氨基酸替换可能与线粒体功能障碍有关，并可能是ANE发病的易感因素。

Cytokine storm may play an important role in the pathomechanismof acute necrotizing encephalopathy (ANE) recognized in Japan. It is still unknownwhether ANE is caused by a single gene mutation such as RANBP2. We conducted geneticanalysis of COX genes, which are the potential binding proteins of RANBP2 and co-operateon mitochondrial electron transfer system. We could not detect the mutation in COX11 and COX17 in 24 ANE patients. We found a heterozygous amino acid substitution in exon 3 of COX10 in a case with ANE. Three patients had minor allele A of non-synonymousrs2231682 in COX15 (MAF <0.01). We suggested that these amino acid substitutions ofCOXs may relevant to mitochondrial dysfunction and predispose to the onset of ANE.