BACKGROUND Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved. METHODS We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory. RESULTS A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy. CONCLUSION We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT.

中文翻译：

---

鉴定患有常染色体显性遗传夏科特-玛丽齿病的家庭中罕见的SEPT9变异体。

背景技术夏科-玛丽齿病（CMT）是最普遍遗传的神经系统疾病之一。越来越多的涉及神经胶质和神经元功能的基因与CMT的不同亚型相关，从而导致对病理生理机制的诊断和了解得到改善。但是，一些患者和家属在遗传上仍未解决。方法我们报道了一个德国家庭，包括三个世代中的四个受影响成员，他们的CMT表型伴有认知缺陷，主要涉及视觉能力和情节记忆。结果全面的临床表征和随后的诊断方法揭示了杂合的罕见SEPT9错义变体c.1406 T> C，p。（Val469Ala），与疾病隔离。SEPT9已与多种细胞内功能相关，例如胞质分裂和膜运输。有趣的是，已知SEPT9突变会导致遗传性神经性肌萎缩症（HNA），这是一种复发性局灶性周围神经病。结论我们首次提出了与CMT表型相关的SEPT9变异体，并建议SEPT9作为CMT中足够的新候选基因。