Peripheral myelin protein 2 (PMP2) is a small protein located on the cytoplasmic side of compact myelin, involved in the lipids transport and in the myelination process. In the last years few families affected with demyelinating Charcot‐Marie‐Tooth neuropathy (CMT1), caused by PMP2 mutations, have been identified. In this study we describe the first case of a PMP2 in‐frame deletion. PMP2 was analyzed by direct sequencing after exclusion of the most frequent CMT‐associated genes by using a next generation sequencing (NGS) genes panel. Sanger sequencing was used for family's segregation analysis. Molecular modeling analysis was used to evaluate the mutation impact on the protein structure. A novel PMP2: p.I50del has been identified in a child with early onset CMT1 and in three affected family members. All family members show an early onset demyelinating neuropathy without other distinguish features. Molecular modeling analysis and in silico evaluations do not suggest a strong impact on the overall protein structure, but a most likely altered protein function. This study suggests the importance to add PMP2 in CMT NGS genes panels or, at most, to test it after major CMT1 genes exclusion, due to the lack of diagnostic‐addressing additional features.

中文翻译：

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外周髓磷脂蛋白2中新的框架内异亮氨酸缺失导致的早发性脱髓鞘性Charcot-Marie-Tooth病

外周髓磷脂蛋白2（PMP2）是位于紧密髓磷脂的细胞质侧的一种小蛋白，参与脂质转运和髓鞘形成过程。在过去的几年中，很少有人发现由PMP2突变引起的脱髓鞘性Charcot-Marie-Tooth神经病（CMT1）影响的家庭。在这项研究中，我们描述了PMP2帧内删除的第一种情况。PMP2通过使用下一代测序（NGS）基因组排除最常见的CMT相关基因后，通过直接测序进行分析。Sanger测序用于家庭隔离分析。使用分子建模分析来评估突变对蛋白质结构的影响。在患有CMT1早期发作的儿童和三个受影响的家庭成员中发现了一种新型PMP2：p.I50del。所有家庭成员均表现出早期发作的脱髓鞘性神经病，无其他明显特征。分子模型分析和计算机模拟评估并未显示出对整体蛋白质结构的强烈影响，但最有可能改变了蛋白质功能。这项研究表明添加PMP2的重要性 在CMT NGS基因组中进行检测，或者最多在排除主要CMT1基因后进行检测，原因是缺少诊断寻址的其他功能。