{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T07:46:17Z","timestamp":1773215177011,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III, (ISCIII)","award":["PI18_01374"],"award-info":[{"award-number":["PI18_01374"]}]},{"name":"Instituto de Salud Carlos III, (ISCIII)","award":["PI20_00057"],"award-info":[{"award-number":["PI20_00057"]}]},{"name":"Instituto de Salud Carlos III, (ISCIII)","award":["B2017\/BMD-3721"],"award-info":[{"award-number":["B2017\/BMD-3721"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (Madrid, Spain), (co-funded by European Regional Development Fund \u201cA way to make Europe\u201d)","award":["PI18_01374"],"award-info":[{"award-number":["PI18_01374"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (Madrid, Spain), (co-funded by European Regional Development Fund \u201cA way to make Europe\u201d)","award":["PI20_00057"],"award-info":[{"award-number":["PI20_00057"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (Madrid, Spain), (co-funded by European Regional Development Fund \u201cA way to make Europe\u201d)","award":["B2017\/BMD-3721"],"award-info":[{"award-number":["B2017\/BMD-3721"]}]},{"name":"ISCIII-CIBERER contract","award":["PI18_01374"],"award-info":[{"award-number":["PI18_01374"]}]},{"name":"ISCIII-CIBERER contract","award":["PI20_00057"],"award-info":[{"award-number":["PI20_00057"]}]},{"name":"ISCIII-CIBERER contract","award":["B2017\/BMD-3721"],"award-info":[{"award-number":["B2017\/BMD-3721"]}]},{"name":"Raregenomics-CM Network","award":["PI18_01374"],"award-info":[{"award-number":["PI18_01374"]}]},{"name":"Raregenomics-CM Network","award":["PI20_00057"],"award-info":[{"award-number":["PI20_00057"]}]},{"name":"Raregenomics-CM Network","award":["B2017\/BMD-3721"],"award-info":[{"award-number":["B2017\/BMD-3721"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We report a neonatal patient with hypertrophic cardiomyopathy (HCM), lactic acidosis and isolated complex I deficiency. Using a customized next-generation sequencing panel, we identified a novel hemizygous variant c.338G&gt;A in the X-linked NDUFB11 gene that encodes the NADH: ubiquinone oxidoreductase subunit B11 of the mitochondrial respiratory chain (MRC) complex I (CI). Molecular and functional assays performed in the proband\u2019s target tissues\u2014skeletal and heart muscle\u2014showed biochemical disturbances of the MRC, suggesting a pathogenic role for this variant. In silico analyses initially predicted an amino acid missense change p.(Arg113Lys) in the NDUFB11 CI subunit. However, we showed that the molecular effect of the c.338G&gt;A variant, which is located at the last nucleotide of exon 2 of the NDUFB11 gene in the canonical \u2018short\u2019 transcript (sized 462 bp), instead causes a splicing defect triggering the up-regulation of the expression of an alternative \u2018long\u2019 transcript (sized 492 bp) that can also be detected in the control individuals. Our results support the hypothesis that the canonical \u2018short\u2019 transcript is required for the proper NDUFB11 protein synthesis, which is essential for optimal CI assembly and activity, whereas the longer alternative transcript seems to represent a non-functional, unprocessed splicing intermediate. Our results highlight the importance of characterizing the molecular effect of new variants in the affected patient\u2019s tissues to demonstrate their pathogenicity and association with the clinical phenotypes.<\/jats:p>","DOI":"10.3390\/ijms24021743","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:29:55Z","timestamp":1673836195000},"page":"1743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene"],"prefix":"10.3390","volume":"24","author":[{"given":"Guillermo","family":"Amate-Garc\u00eda","sequence":"first","affiliation":[{"name":"Grupo de Enfermedades Mitocondriales y Neuromusculares, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Juliana","family":"Ballesta-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"},{"name":"Secci\u00f3n de Gen\u00e9tica M\u00e9dica, Servicio de Pediatr\u00eda, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Pascual Parrilla, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-7574","authenticated-orcid":false,"given":"Pablo","family":"Serrano-Lorenzo","sequence":"additional","affiliation":[{"name":"Grupo de Enfermedades Mitocondriales y Neuromusculares, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-4399","authenticated-orcid":false,"given":"Roc\u00edo","family":"Garrido-Moraga","sequence":"additional","affiliation":[{"name":"Grupo de Enfermedades Mitocondriales y Neuromusculares, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-362X","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Gonz\u00e1lez-Quintana","sequence":"additional","affiliation":[{"name":"Grupo de Enfermedades Mitocondriales y Neuromusculares, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, 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