{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:52:36Z","timestamp":1786978356768,"version":"build-2736575974"},"reference-count":11,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT093205MA"],"award-info":[{"award-number":["WT093205MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT104033AIA"],"award-info":[{"award-number":["WT104033AIA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Biallelic loss\u2010of\u2010function\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To fully characterize, both phenotypically and genotypically,\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      \u2010related mitochondrial disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine unreported\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and\/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06), optic atrophy (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a02), or was unremarkable (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01). All carried homozygous truncating\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      variants, three of which are novel.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our case series expands phenotype\u2013genotype correlations in\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      \u2010associated mitochondrial disease, providing evidence of intra\u2010 and inter\u2010familial clinical heterogeneity for the same variant. It confirms\n                      <jats:italic>NDUFA12<\/jats:italic>\n                      variants should be included in the diagnostic workup of Leigh\/Leigh\u2010like syndromes \u2013 particularly with dystonia \u2013 as well as isolated optic atrophy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mdc3.13398","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T08:29:20Z","timestamp":1639729760000},"page":"218-228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biallelic Loss\u2010of\u2010Function\n                    <scp>\n                      <i>NDUFA12<\/i>\n                    <\/scp>\n                    Variants Cause a Wide Phenotypic Spectrum from Leigh\/Leigh\u2010Like Syndrome to Isolated Optic Atrophy"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4706-6245","authenticated-orcid":false,"given":"Francesca","family":"Magrinelli","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London United Kingdom"},{"name":"Department of Neurosciences, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Cali","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius Lopes","family":"Braga","sequence":"additional","affiliation":[{"name":"Department of Neurology Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulu\u00e7","family":"Yis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics Dokuz Eyl\u00fcl University Faculty of Medicine  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda","family":"Tomoum","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Shamseldin","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Raiman","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Disease Birmingham Children's Hospital  Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kernstock","sequence":"additional","affiliation":[{"name":"Center for Ophthalmology Institute for Ophthalmic Research, University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4565-5898","authenticated-orcid":false,"given":"Fl\u00e1vio Moura","family":"Rezende Filho","sequence":"additional","affiliation":[{"name":"Department of Neurology Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando Graziani Povoas","family":"Barsottini","sequence":"additional","affiliation":[{"name":"Department of Neurology Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsebet","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Tamim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Sch\u00e4ferhoff","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Maria Ferraz","family":"Sallum","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Universidade Federal de S\u00e3o Paulo (UNIFESP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha S.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Institute National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Neurology Universidade de S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"},{"name":"Mendelics Genomic Analysis  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-286X","authenticated-orcid":false,"given":"Kailash P.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Wissinger","sequence":"additional","affiliation":[{"name":"Center for Ophthalmology Institute for Ophthalmic Research, University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Sergeant","sequence":"additional","affiliation":[{"name":"Oxford Genetics Laboratories Oxford University Hospitals NHS Foundation Trust  Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Centre for Rare Diseases University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge, John Van Geest Cambridge Centre for Brain Repair  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semra","family":"Hiz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics Dokuz Eyl\u00fcl University Faculty of Medicine  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fowzan S.","family":"Alkuraya","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"},{"name":"Department of Anatomy and Cell Biology College of Medicine, Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1672-8894","authenticated-orcid":false,"given":"Jos\u00e9 Luiz","family":"Pedroso","sequence":"additional","affiliation":[{"name":"Department of Neurology Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London  London United 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