Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report
Leigh syndrome (LS) usually presents as an early onset mitochondrial encephalopathy characterized by bilateral symmetric lesions in the basal ganglia and cerebral stem. More than 75 genes have been associated with this condition, including genes involved in the biogenesis of mitochondrial complex I...
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MDPI AG
2020-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/8/855 |
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| author | Adrián González-Quintana Inés García-Consuegra Amaya Belanger-Quintana Pablo Serrano-Lorenzo Alejandro Lucia Alberto Blázquez Jorge Docampo Cristina Ugalde María Morán Joaquín Arenas Miguel A. Martín |
| author_facet | Adrián González-Quintana Inés García-Consuegra Amaya Belanger-Quintana Pablo Serrano-Lorenzo Alejandro Lucia Alberto Blázquez Jorge Docampo Cristina Ugalde María Morán Joaquín Arenas Miguel A. Martín |
| author_sort | Adrián González-Quintana |
| collection | DOAJ |
| description | Leigh syndrome (LS) usually presents as an early onset mitochondrial encephalopathy characterized by bilateral symmetric lesions in the basal ganglia and cerebral stem. More than 75 genes have been associated with this condition, including genes involved in the biogenesis of mitochondrial complex I (CI). In this study, we used a next-generation sequencing (NGS) panel to identify two novel biallelic variants in the NADH:ubiquinone oxidoreductase subunit A13 (<i>NDUFA13</i>) gene in a patient with isolated CI deficiency in skeletal muscle. Our patient, who represents the second family report with mutations in the CI NDUFA13 subunit, presented with LS lesions in brain magnetic resonance imaging, mild hypertrophic cardiomyopathy, and progressive spastic tetraparesis. This phenotype manifestation is different from that previously described in the first <i>NDUFA13</i> family, which was predominantly characterized by neurosensorial symptoms. Both in silico pathogenicity predictions and oxidative phosphorylation (OXPHOS) functional findings in patient’s skin fibroblasts (delayed cell growth, isolated CI enzyme defect, decreased basal and maximal oxygen consumption and as well as ATP production, together with markedly diminished levels of the NDUFA13 protein, CI, and respirasomes) suggest that these novel variants in the <i>NDUFA13</i> gene are the underlying cause of the CI defect, expanding the genetic heterogeneity of LS. |
| first_indexed | 2024-03-10T18:12:32Z |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T18:12:32Z |
| publishDate | 2020-07-01 |
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| series | Genes |
| spelling | doaj.art-e6a9d620d273412bbaf3ad94b456cc7d2023-11-20T08:01:54ZengMDPI AGGenes2073-44252020-07-0111885510.3390/genes11080855Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family ReportAdrián González-Quintana0Inés García-Consuegra1Amaya Belanger-Quintana2Pablo Serrano-Lorenzo3Alejandro Lucia4Alberto Blázquez5Jorge Docampo6Cristina Ugalde7María Morán8Joaquín Arenas9Miguel A. Martín10Laboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainServicio de Pediatría, Enfermedades Metabólicas Hereditarias, Hospital Universitario Ramón y Cajal, 28034 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainFacultad de Ciencias del Deporte, Universidad Europea, 28670 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLaboratorio de Enfermedades Mitocondriales y Neurometabólicas, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, SpainLeigh syndrome (LS) usually presents as an early onset mitochondrial encephalopathy characterized by bilateral symmetric lesions in the basal ganglia and cerebral stem. More than 75 genes have been associated with this condition, including genes involved in the biogenesis of mitochondrial complex I (CI). In this study, we used a next-generation sequencing (NGS) panel to identify two novel biallelic variants in the NADH:ubiquinone oxidoreductase subunit A13 (<i>NDUFA13</i>) gene in a patient with isolated CI deficiency in skeletal muscle. Our patient, who represents the second family report with mutations in the CI NDUFA13 subunit, presented with LS lesions in brain magnetic resonance imaging, mild hypertrophic cardiomyopathy, and progressive spastic tetraparesis. This phenotype manifestation is different from that previously described in the first <i>NDUFA13</i> family, which was predominantly characterized by neurosensorial symptoms. Both in silico pathogenicity predictions and oxidative phosphorylation (OXPHOS) functional findings in patient’s skin fibroblasts (delayed cell growth, isolated CI enzyme defect, decreased basal and maximal oxygen consumption and as well as ATP production, together with markedly diminished levels of the NDUFA13 protein, CI, and respirasomes) suggest that these novel variants in the <i>NDUFA13</i> gene are the underlying cause of the CI defect, expanding the genetic heterogeneity of LS.https://www.mdpi.com/2073-4425/11/8/855mitochondrial complex I deficiency<i>NDUFA13</i> genemitochondrial OXPHOS dysfunctionLeigh syndromeOXPHOS assemblyOXPHOS diagnosis |
| spellingShingle | Adrián González-Quintana Inés García-Consuegra Amaya Belanger-Quintana Pablo Serrano-Lorenzo Alejandro Lucia Alberto Blázquez Jorge Docampo Cristina Ugalde María Morán Joaquín Arenas Miguel A. Martín Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report Genes mitochondrial complex I deficiency <i>NDUFA13</i> gene mitochondrial OXPHOS dysfunction Leigh syndrome OXPHOS assembly OXPHOS diagnosis |
| title | Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report |
| title_full | Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report |
| title_fullStr | Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report |
| title_full_unstemmed | Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report |
| title_short | Novel <i>NDUFA13</i> Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report |
| title_sort | novel i ndufa13 i mutations associated with oxphos deficiency and leigh syndrome a second family report |
| topic | mitochondrial complex I deficiency <i>NDUFA13</i> gene mitochondrial OXPHOS dysfunction Leigh syndrome OXPHOS assembly OXPHOS diagnosis |
| url | https://www.mdpi.com/2073-4425/11/8/855 |
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