XPR1 mutations are a rare cause of primary familial brain calcification
XPR1 mutations are a rare cause of primary familial brain calcification
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DOI：
10.1007/s00415-016-8166-4
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发表时间：
2016-08-01
影响因子：
6
通讯作者：
Nicolas, Gael
中科院分区：
文献类型：
--
作者：
Anheim, Mathieu;Lopez-Sanchez, Uriel;Nicolas, Gael
最近在原发性家族性脑钙化 (PFBC) 患者中发现了 XPR1（一种编码无机磷酸盐输出蛋白的基因）的突变。使用 Sanger 测序，我们在 18 名无关的 PFBC 患者中筛查了 XPR1，且无 SLC20A2、PDGFB 或 PDGFRB 突变。 XPR1 变体在体外生理互补测定中进行了测试，并在体外评估了患者血细胞的磷酸盐输出。我们在一名 41 岁男性中发现了一种新的 c.260T > C, p.(Leu87Pro) XPR1 变异，该男性主诉小写症和构音障碍，并表现出轻度帕金森症、小脑性共济失调和执行功能障碍。脑部 I-123-Ioflupan 闪烁扫描显示多巴胺能神经元明显丧失。患者的外周血细胞表现出磷酸盐输出减少。我们引入突变的 XPR1 在细胞表面无法检测到，并且不会导致磷酸盐输出。这些结果证实，XPR1 介导的磷酸盐输出功能的丧失会导致 PFBC（在其他基因呈阴性的病例中发生率不到 8%），并可能导致帕金森病。
Mutations in XPR1, a gene encoding an inorganic phosphate exporter, have recently been identified in patients with primary familial brain calcification (PFBC). Using Sanger sequencing, we screened XPR1 in 18 unrelated patients with PFBC and no SLC20A2, PDGFB, or PDGFRB mutation. XPR1 variants were tested in an in vitro physiological complementation assay and patient blood cells were assessed ex vivo for phosphate export. We identified a novel c.260T > C, p.(Leu87Pro) XPR1 variant in a 41-year-old man complaining of micrographia and dysarthria and demonstrating mild parkinsonism, cerebellar ataxia and executive dysfunction. Brain I-123-Ioflupane scintigraphy showed marked dopaminergic neuron loss. Peripheral blood cells from the patient exhibited decreased phosphate export. XPR1 in which we introduced the mutation was not detectable at the cell surface and did not lead to phosphate export. These results confirm that loss of XPR1-mediated phosphate export function causes PFBC, occurring in less than 8 % of cases negative for the other genes, and may be responsible for parkinsonism.