Vinci Mirella, Vitello Girolamo Aurelio, Greco Donatella, Treccarichi Simone, Ragalmuto Alda, Musumeci Antonino, Fallea Antonio, Federico Concetta, Calì Francesco, Saccone Salvatore, Elia Maurizio
Oasi Research Institute-IRCCS, 94018 Troina, Italy.
Department of Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, Italy.
Curr Issues Mol Biol. 2024 Jan 29;46(2):1150-1163. doi: 10.3390/cimb46020073.
Ion channelopathies result from impaired ion channel protein function, due to mutations affecting ion transport across cell membranes. Over 40 diseases, including neuropathy, pain, migraine, epilepsy, and ataxia, are associated with ion channelopathies, impacting electrically excitable tissues and significantly affecting skeletal muscle. Gene mutations affecting transmembrane ionic flow are strongly linked to skeletal muscle disorders, particularly myopathies, disrupting muscle excitability and contraction. Electromyography (EMG) analysis performed on a patient who complained of weakness and fatigue revealed the presence of primary muscular damage, suggesting an early-stage myopathy. Whole exome sequencing (WES) did not detect potentially causative variants in known myopathy-associated genes but revealed a novel homozygous deletion of the gene likely disrupting protein function. The gene, predominantly expressed in skeletal muscle, is an ATP-gated ion channel receptor belonging to the purinergic receptors (P2RX) family. In addition, STRING pathways suggested a correlation with more proteins having a plausible role in myopathy. No previous studies have reported the implication of this gene in myopathy. Further studies are needed on patients with a defective ion channel pathway, and the use of in vitro functional assays in suppressing gene expression will be required to validate its functional role.
离子通道病是由于影响离子跨细胞膜转运的突变导致离子通道蛋白功能受损所致。超过40种疾病，包括神经病变、疼痛、偏头痛、癫痫和共济失调，都与离子通道病有关，影响电兴奋性组织并显著影响骨骼肌。影响跨膜离子流的基因突变与骨骼肌疾病密切相关，尤其是肌病，会破坏肌肉兴奋性和收缩功能。对一名主诉虚弱和疲劳的患者进行的肌电图（EMG）分析显示存在原发性肌肉损伤，提示早期肌病。全外显子组测序（WES）未在已知的肌病相关基因中检测到潜在的致病变异，但发现一个基因的新型纯合缺失可能破坏蛋白质功能。该基因主要在骨骼肌中表达，是一种属于嘌呤能受体（P2RX）家族的ATP门控离子通道受体。此外，STRING通路表明与更多在肌病中可能起作用的蛋白质存在相关性。此前没有研究报道过该基因与肌病的关联。需要对离子通道途径有缺陷的患者进行进一步研究，并且需要使用体外功能试验来抑制该基因表达，以验证其功能作用。
