Elastin microfibril interface-located proteins (EMILINs) are extracellular matrix glycoproteins implicated in elastogenesis and cell proliferation. Recently, a missense mutation in the EMILIN1 gene has been associated with autosomal dominant connective tissue disorder and motor-sensory neuropathy in a single family. We identified by whole exome sequencing a novel heterozygous EMILIN1 mutation c.748C>T [p.R250C] located in the coiled coil forming region of the protein, in four affected members of an autosomal dominant family presenting a distal motor neuropathy phenotype. In affected patient a sensory nerve biopsy showed slight and unspecific changes in the number and morphology of myelinated fibers. Immunofluorescence study of a motor nerve within a muscle biopsy documented the presence of EMILIN-1 in nerve structures. Skin section and skin derived fibroblasts displayed a reduced extracellular deposition of EMILIN-1 protein with a disorganized network of poorly ramified fibers in comparison with controls. Downregulation of emilin1a in zebrafish displayed developmental delay, locomotion defects, and abnormal axonal arborization from spinal cord motor neurons. The phenotype was complemented by wild-type zebrafish emilin1a, and partially the human wild-type EMILIN1 cRNA, but not by the cRNA harboring the novel c.748C>T [p.R250C]. These data suggest a role of EMILIN-1 in the pathogenesis of diseases affecting the peripheral nervous system.

中文翻译：

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与新的EMILIN1突变相关的远端运动神经病。

弹性蛋白微纤维界面定位蛋白（EMILINs）是细胞外基质糖蛋白，与弹性发生和细胞增殖有关。最近，EMILIN1基因的一个错义突变与一个家族的常染色体显性结缔组织疾病和运动感觉神经病有关。我们通过全外显子组测序鉴定了位于常染色体显性家族的四个受影响成员中的新型杂合性EMILIN1突变c.748C> T [p.R250C]，位于蛋白质的卷曲螺旋形成区域，呈现远端运动神经病表型。在受影响的患者中，感觉神经活检显示髓鞘纤维的数量和形态有轻微和非特异性的变化。肌肉活检中运动神经的免疫荧光研究表明，神经结构中存在EMILIN-1。与对照相比，皮肤切片和皮肤来源的成纤维细胞显示出EMILIN-1蛋白的细胞外沉积减少，分支不良的纤维网络杂乱无章。斑马鱼中emilin1a的下调显示发育延迟，运动缺陷和脊髓运动神经元引起的轴突乔化异常。该表型由野生型斑马鱼emilin1a和部分人野生型EMILIN1 cRNA进行了补充，但没有包含新型c.748C> T [p.R250C]的cRNA进行了补充。这些数据表明EMILIN-1在影响外周神经系统的疾病的发病机理中的作用。斑马鱼中emilin1a的下调显示发育延迟，运动缺陷和脊髓运动神经元引起的轴突乔化异常。该表型由野生型斑马鱼emilin1a和部分人野生型EMILIN1 cRNA进行了补充，但没有包含新型c.748C> T [p.R250C]的cRNA进行了补充。这些数据表明EMILIN-1在影响外周神经系统的疾病的发病机理中的作用。斑马鱼中emilin1a的下调显示发育延迟，运动缺陷和来自脊髓运动神经元的异常轴突乔化。该表型由野生型斑马鱼emilin1a和部分人野生型EMILIN1 cRNA进行了补充，但没有包含新型c.748C> T [p.R250C]的cRNA进行了补充。这些数据表明EMILIN-1在影响外周神经系统的疾病的发病机理中的作用。