A novel mutation in SLC39A14 causing hypermanganesemia associated with infantile onset dystonia
A novel mutation in SLC39A14 causing hypermanganesemia associated with infantile onset dystonia
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DOI：
10.1002/jgm.3012
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Faruq, Mohammed
中科院分区：
文献类型：
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作者：
Juneja, Monica;Shamim, Uzma;Faruq, Mohammed
BackgroundSLC39A14突变导致隐性锰（Mn）代谢障碍，表现为儿童期发作的进行性神经变性，其特征为帕金森综合征和肌张力障碍。我们描述了一个家庭，其中一个受影响的儿童进行性神经变性的历史表现出肌张力障碍的症状，血锰水平升高，苍白球和齿状核信号强度改变。通过全外显子组测序对该患儿的病理进行了遗传学研究，从而确定了SLC39A14中的一个新的纯合突变。结果SLC39A14中的一个新的纯合突变的Insilico模型预测它是有害的，通过蛋白质结构的跨膜不稳定性影响Mn结合和金属转运。SLC39A14中其他报告的突变的临床特征也进行了审查，在我们的情况下，临床频谱符合所描述的神经系统abnormality.ConclusionsWe的结论是，在我们的情况下，SLC39A14中确定的突变是一种新的变异与隐性疾病的高镁血症和肌张力障碍。
BackgroundMutations in SLC39A14 cause a recessive disorder of manganese (Mn) metabolism that manifests as childhood onset progressive neurodegeneration characterized by parkinsonism and dystonia.MethodsThe present study genetically investigated a case of hypermanganesemia. We describe a family where an affected child with a history of progressive neurodegeneration showed symptoms of dystonia with increased levels of blood Mn and altered signal intensities in globus pallidus and dentate nucleus. Whole exome sequencing was conducted to genetically investigate the pathology in the child, which allowed us to identify a novel homozygous causal mutation in SLC39A14.ResultsInsilico modeling of the novel homozygous causal mutation in SLC39A14 predicted that it was deleterious, affecting Mn binding and transportation of metal by transmembrane instability of the protein structure. The clinical features of other reported mutations in SLC39A14 were also reviewed and the clinical spectrum in our case conforms to the described neurological abnormalities.ConclusionsWe conclude that the mutation identified in SLC39A14 in our case is a novel variation linked to recessive disorders of hypermaganesemia and dystonia.