{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:01:34Z","timestamp":1775260894743,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["21466"],"award-info":[{"award-number":["21466"]}],"id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["un"],"award-info":[{"award-number":["un"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerium f\u00fcr Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen","award":["un"],"award-info":[{"award-number":["un"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NME-GPS"],"award-info":[{"award-number":["NME-GPS"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations in the SPATA5 gene are associated with epilepsy, hearing loss and mental retardation syndrome (EHLMRS). While SPATA5 is ubiquitously expressed and is attributed a role within mitochondrial morphogenesis during spermatogenesis, there is only limited knowledge about the associated muscular and molecular pathology. This study reports on a comprehensive workup of muscular pathology, including proteomic profiling and microscopic studies, performed on an 8-year-old girl with typical clinical presentation of EHLMRS, where exome analysis revealed two clinically relevant, compound-heterozygous variants in SPATA5. Proteomic profiling of a quadriceps biopsy showed the dysregulation of 82 proteins, out of which 15 were localized in the mitochondrion, while 19 were associated with diseases presenting with phenotypical overlap to EHLMRS. Histological staining of our patient\u2019s muscle biopsy hints towards mitochondrial pathology, while the identification of dysregulated proteins attested to the vulnerability of the cell beyond the mitochondria. Through our study we provide insights into the molecular etiology of EHLMRS and provide further evidence for a muscle pathology associated with SPATA5 deficiency, including a pathological histochemical pattern accompanied by dysregulated protein expression.<\/jats:p>","DOI":"10.3390\/ijms22157835","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T22:35:31Z","timestamp":1626993331000},"page":"7835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-2746","authenticated-orcid":false,"given":"Frederik","family":"Braun","sequence":"first","affiliation":[{"name":"Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften\u2014ISAS e.V., 44139 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Sickmann","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften\u2014ISAS e.V., 44139 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore","family":"Marteau","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swantje","family":"Hertel","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Disorders, 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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany"},{"name":"Helmholtz Zentrum M\u00fcnchen\u2014German Research Center for Environmental Health, Institute of Neurogenomics, 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1968-8103","authenticated-orcid":false,"given":"Saskia","family":"Wortmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Della Marina","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Disorders, Centre for Translational Neuro- and 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