Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy
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 s...
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MDPI AG
2024-01-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/46/2/73 |
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| author | Mirella Vinci Girolamo Aurelio Vitello Donatella Greco Simone Treccarichi Alda Ragalmuto Antonino Musumeci Antonio Fallea Concetta Federico Francesco Calì Salvatore Saccone Maurizio Elia |
| author_facet | Mirella Vinci Girolamo Aurelio Vitello Donatella Greco Simone Treccarichi Alda Ragalmuto Antonino Musumeci Antonio Fallea Concetta Federico Francesco Calì Salvatore Saccone Maurizio Elia |
| author_sort | Mirella Vinci |
| collection | DOAJ |
| description | 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 <i>P2RX6</i> gene likely disrupting protein function. The <i>P2RX6</i> 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 <i>P2RX6</i> gene expression will be required to validate its functional role. |
| first_indexed | 2024-03-07T22:38:12Z |
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| issn | 1467-3037 1467-3045 |
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| last_indexed | 2024-03-07T22:38:12Z |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-ec923136ff84447eb001c4b042a48c4c2024-02-23T15:12:35ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452024-01-014621150116310.3390/cimb46020073Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in MyopathyMirella Vinci0Girolamo Aurelio Vitello1Donatella Greco2Simone Treccarichi3Alda Ragalmuto4Antonino Musumeci5Antonio Fallea6Concetta Federico7Francesco Calì8Salvatore Saccone9Maurizio Elia10Oasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyDepartment of Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyDepartment of Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyIon 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 <i>P2RX6</i> gene likely disrupting protein function. The <i>P2RX6</i> 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 <i>P2RX6</i> gene expression will be required to validate its functional role.https://www.mdpi.com/1467-3045/46/2/73early-onset myopathyion channelopathyP2X receptorswhole exome sequencing<i>P2RX6</i> geneskeletal muscle |
| spellingShingle | Mirella Vinci Girolamo Aurelio Vitello Donatella Greco Simone Treccarichi Alda Ragalmuto Antonino Musumeci Antonio Fallea Concetta Federico Francesco Calì Salvatore Saccone Maurizio Elia Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy Current Issues in Molecular Biology early-onset myopathy ion channelopathy P2X receptors whole exome sequencing <i>P2RX6</i> gene skeletal muscle |
| title | Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy |
| title_full | Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy |
| title_fullStr | Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy |
| title_full_unstemmed | Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy |
| title_short | Next Generation Sequencing and Electromyography Reveal the Involvement of the <i>P2RX6</i> Gene in Myopathy |
| title_sort | next generation sequencing and electromyography reveal the involvement of the i p2rx6 i gene in myopathy |
| topic | early-onset myopathy ion channelopathy P2X receptors whole exome sequencing <i>P2RX6</i> gene skeletal muscle |
| url | https://www.mdpi.com/1467-3045/46/2/73 |
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