Živković Sasha A, Nowak Richard J, DiCapua Daniel
Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; CMT Program at Yale University, Department of Neurology, Yale University, New Haven, CT, USA.
Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Neuromuscul Disord. 2025 Feb;47:105254. doi: 10.1016/j.nmd.2024.105254. Epub 2024 Nov 29.
Axonal Charcot-Marie-Tooth disease (CMT2) and distal hereditary motor neuropathy (dHMN) are associated with a heterogeneous group of genes encoding proteins that are involved in axonal transport, control of RNA metabolism, mitochondrial dynamics and DNA repair. VRK1 (vaccinia-related kinase 1) is a serine/threonine kinase which is widely expressed in human tissue and plays a role in RNA maturation and processing and in DNA damage response. Variants of VRK1 have been associated with neurodevelopmental and neuromuscular disorders including pontocerebellar hypoplasia, motor neuron disorders and distal hereditary motor neuropathy. We present 3 cases of VRK1-associated neuromuscular disorders without neurodevelopmental abnormalities including CMT2 associated with homozygous variant of VRK1 at Arg387His and dHMN with combination of heterozygous variants at Arg133His and Asp243Asn. While our case series expands the clinical spectrum of VRK1-associated neuromuscular disorders, additional studies are needed to elucidate pathophysiology of neuromuscular disorders associated with VRK1 variants.
轴索性遗传性运动感觉神经病2型（CMT2）和远端遗传性运动神经病（dHMN）与一组异质性基因相关，这些基因编码参与轴突运输、RNA代谢调控、线粒体动力学和DNA修复的蛋白质。VRK1（痘苗相关激酶1）是一种丝氨酸/苏氨酸激酶，在人体组织中广泛表达，在RNA成熟和加工以及DNA损伤反应中发挥作用。VRK1的变异与神经发育和神经肌肉疾病相关，包括脑桥小脑发育不全、运动神经元疾病和远端遗传性运动神经病。我们报告了3例与VRK1相关的神经肌肉疾病病例，无神经发育异常，包括与VRK1基因第387位精氨酸突变为组氨酸的纯合变异相关的CMT2，以及与第133位精氨酸突变为组氨酸和第243位天冬氨酸突变为天冬酰胺的杂合变异组合相关的dHMN。虽然我们的病例系列扩展了与VRK1相关的神经肌肉疾病的临床谱，但仍需要进一步研究以阐明与VRK1变异相关的神经肌肉疾病的病理生理学。
