Peripheral myelin protein 22 (PMP22) related neuropathies account for over 50% of inherited peripheral neuropathies. A gene copy variation results in CMT1A (duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; single deletion). Point mutations comprise both phenotypes. The underlying pathological mechanisms are incompletely understood and biallelic mutations of PMP22 are very rare. We describe a 9‐year‐old girl who presented before the age of 1 year with severe locomotor delay. She now requires support for standing and walking in view of her severe sensory ataxia. Strikingly, her muscle power and bulk are close to normal in all segments. Nerve conduction studies showed sensory‐motor velocities below 5 m/s. Genetic analysis revealed a homozygous sequence change in the PMP22 gene causing the loss of termination codon (c.483A > G; p.[*161Trpext*10]), extending the protein by 9 amino acids. Both heterozygous parents have neurophysiological abnormalities consistent with HNPP, consistent with this being a loss‐of‐function mutation. PMP22‐deficient human models are rare but important to decipher the physiological function of the PMP22 protein in vivo. The predominance of large fiber sensory involvement in this and other rare similar cases suggests a pivotal role played by PMP22 in the embryogenesis of dorsal root ganglia in humans.

中文翻译：

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一种将外周髓鞘蛋白 22 延长 9 个氨基酸的新型纯合变体导致早发性 Charcot-Marie-Tooth 病，主要是严重的感觉性共济失调。

外周髓鞘蛋白 22 (PMP22) 相关的神经病占遗传性外周神经病的 50% 以上。基因拷贝变异导致 CMT1A（重复）和遗传性神经病，易患压力性麻痹（HNPP；单一缺失）。点突变包括两种表型。潜在的病理机制尚不完全清楚，PMP22 的双等位基因突变非常罕见。我们描述了一名 9 岁女孩，她在 1 岁前出现严重的运动迟缓。鉴于她严重的感觉共济失调，她现在需要支持站立和行走。引人注目的是，她的肌肉力量和体积在所有部分都接近正常。神经传导研究显示感觉运动速度低于 5 m/s。遗传分析揭示了纯合子序列的变化PMP22基因导致终止密码子丢失（c.483A > G；p.[*161Trpext*10]），将蛋白质延长 9 个氨基酸。杂合子父母都具有与 HNPP 一致的神经生理异常，这与这是功能丧失突变一致。PMP22 缺陷的人体模型很少见，但对于破译 PMP22 蛋白在体内的生理功能很重要。在这种和其他罕见的类似病例中大纤维感觉参与的优势表明 PMP22 在人类背根神经节的胚胎发生中发挥了关键作用。