与VRK1变异相关的CMT2和远端遗传性运动神经病变：病例系列

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-02-01 DOI:10.1016/j.nmd.2024.105254

Sasha A. Živković , Richard J. Nowak , Daniel DiCapua

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引用次数: 0

摘要

轴突沙科-玛丽-图斯病（CMT2）和远端遗传性运动神经病（dHMN）与一组异质基因编码蛋白有关，这些蛋白参与轴突运输、RNA代谢控制、线粒体动力学和DNA修复。VRK1（牛痘相关激酶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损伤反应中起作用。VRK1的变异与神经发育和神经肌肉疾病有关，包括桥小脑发育不全、运动神经元疾病和远端遗传性运动神经病变。我们报告了3例无神经发育异常的VRK1相关神经肌肉疾病，包括CMT2与VRK1 Arg387His和dHMN纯合变异以及Arg133His和Asp243Asn杂合变异的组合相关。虽然我们的病例系列扩大了VRK1相关神经肌肉疾病的临床范围，但还需要进一步的研究来阐明与VRK1变异相关的神经肌肉疾病的病理生理学。

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CMT2 and distal hereditary motor neuropathy associated with VRK1 variants: Case series

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.

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.