{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T18:56:42Z","timestamp":1774033002474,"version":"3.50.1"},"reference-count":15,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AFM-t\u00e9l\u00e9thon"},{"name":"Association pour le d\u00e9veloppement de la neurog\u00e9n\u00e9tique"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>X-linked Myopathy with Excessive Autophagy (XMEA) is a rare autophagic vacuolar myopathy caused by mutations in the Vacuolar ATPase assembly factor VMA21 gene; onset usually occurs during childhood and rarely occurs during adulthood. We described a 22-year-old patient with XMEA, whose onset was declared at 11 through gait disorder. He had severe four-limb proximal weakness and amyotrophy, and his proximal muscle MRC score was between 2 and 3\/5 in four limbs; creatine kinase levels were elevated (1385 IU\/L), and electroneuromyography and muscle MRI were suggestive of myopathy. Muscle biopsy showed abnormalities typical of autophagic vacuolar myopathy. We detected a hemizygous, unreported, intronic, single-nucleotide substitution c.164-20T&gt;A (NM_001017980.4) in intron 2 of the VMA21 gene. Fibroblasts derived from this patient displayed a reduced level of VMA21 transcripts (at 40% of normal) and protein, suggesting a pathogenicity related to an alteration of the splicing efficiency associated with an intron retention. This patient with XMEA displayed a severe phenotype (rapid weakness of upper and lower limbs) due to a new intronic variant of VMA21, related to an alteration in the splicing efficiency associated with intron retention, suggesting that phenotype severity is closely related to the residual expression of the VMA21 protein.<\/jats:p>","DOI":"10.3390\/genes13122245","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T04:05:24Z","timestamp":1669781124000},"page":"2245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Intronic Mutation in VMA21 Causing Severe Phenotype of X-Linked Myopathy with Excessive Autophagy\u2014Case Report"],"prefix":"10.3390","volume":"13","author":[{"given":"Antoine","family":"Pegat","sequence":"first","affiliation":[{"name":"Service ENMG et Pathologies Neuromusculaires, H\u00f4pital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France"},{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1709","authenticated-orcid":false,"given":"Nathalie","family":"Streichenberger","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"},{"name":"Service d\u2019anatomopathologie, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Lacoste","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Hermier","sequence":"additional","affiliation":[{"name":"Service de Neuroradiologie, H\u00f4pital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Menassa","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"},{"name":"Service de Biochimie et Biologie Mol\u00e9culaire, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Coudert","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Theuriet","sequence":"additional","affiliation":[{"name":"Service ENMG et Pathologies Neuromusculaires, H\u00f4pital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France"},{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roseline","family":"Froissart","sequence":"additional","affiliation":[{"name":"Service de Biochimie et Biologie Mol\u00e9culaire, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2384-2185","authenticated-orcid":false,"given":"Sophie","family":"Terrone","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francoise","family":"Bouhour","sequence":"additional","affiliation":[{"name":"Service ENMG et Pathologies Neuromusculaires, H\u00f4pital Neurologique P. Wertheimer, Hospices Civils de Lyon, 69500 Bron, France"},{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Michel-Calemard","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"},{"name":"Service de Biochimie et Biologie Mol\u00e9culaire, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"},{"name":"Centre de Biotechnologie Cellulaire, CBC Biotec, Hospices Civils de Lyon-Groupement Est, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-9620","authenticated-orcid":false,"given":"Arnaud","family":"Jacquier","sequence":"additional","affiliation":[{"name":"Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, INMG, Universit\u00e9 Claude Bernard Lyon 1, Facult\u00e9 de M\u00e9decine Lyon Est, 69008 Lyon, France"},{"name":"Centre de Biotechnologie Cellulaire, CBC Biotec, Hospices Civils de Lyon-Groupement Est, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Khandia, R., Dadar, M., Munjal, A., Dhama, K., Karthik, K., Tiwari, R., Yatoo, M.I., Iqbal, H.M.N., Singh, K.P., and Joshi, S.K. 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