{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:30Z","timestamp":1787018370211,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["Intramural Program"],"award-info":[{"award-number":["Intramural Program"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["No 779257"],"award-info":[{"award-number":["No 779257"]}]},{"name":"National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute","award":["UM1 HG008900"],"award-info":[{"award-number":["UM1 HG008900"]}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["R01 HG009141"],"award-info":[{"award-number":["R01 HG009141"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"crossref","award":["MDA577346"],"award-info":[{"award-number":["MDA577346"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union\u2019s Horizon 2020 research","award":["No. 779257"],"award-info":[{"award-number":["No. 779257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,17]]},"abstract":"<jats:p>\n                    Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in\n                    <jats:italic>CIAO1<\/jats:italic>\n                    developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of\n                    <jats:italic>CIAO1<\/jats:italic>\n                    expression reversed all patient-derived cellular abnormalities. Our study identifies\n                    <jats:italic>CIAO1<\/jats:italic>\n                    as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.\n                  <\/jats:p>","DOI":"10.1172\/jci179559","type":"journal-article","created":{"date-parts":[[2024,6,16]],"date-time":"2024-06-16T14:00:39Z","timestamp":1718546439000},"source":"Crossref","is-referenced-by-count":20,"title":["CIAO1 loss of function causes a neuromuscular disorder with compromise of nucleocytoplasmic Fe-S enzymes"],"prefix":"10.1172","volume":"134","author":[{"given":"Nunziata","family":"Maio","sequence":"first","affiliation":[{"name":"Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotem","family":"Orbach","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina T.","family":"Zaharieva","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"T\u00f6pf","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Donkervoort","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinki","family":"Munot","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Mueller","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Willis","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Neuromuscular Disorders, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, United Kingdom."},{"name":"Chester University Medical School, Chester, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-4556","authenticated-orcid":true,"given":"Sumit","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology, Emory University School of Medicine, Georgia, Atlanta, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stojan","family":"Peric","sequence":"additional","affiliation":[{"name":"Department for Neuromuscular Disorders, Neurology Clinic, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Krishnakumar","sequence":"additional","affiliation":[{"name":"Paediatric Neurology, Addenbrooke\u2019s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sniya","family":"Sudhakar","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Great Ormond Street NHS Trust Hospital, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-1119","authenticated-orcid":true,"given":"A. Reghan","family":"Foley","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Silverstein","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganka","family":"Douglas","sequence":"additional","affiliation":[{"name":"GeneDx, LLC, Gaithersburg, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Pais","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"DiTroia","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Grunseich","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3602-0586","authenticated-orcid":true,"given":"Ying","family":"Hu","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sewry","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."},{"name":"Wolfson Centre for Neuromuscular Disorders, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sarkozy","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Straub","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey A.","family":"Rouault","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5930-2324","authenticated-orcid":true,"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.02.001"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2015.06.008"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09989-y"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2019.11.014"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.015"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq301"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80295-6"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600582200"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp239"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3321"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1732541100"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi5224"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219664"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219723"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy004"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2597"},{"key":"B17","doi-asserted-by":"crossref","unstructured":"Chen S, et al. A genome-wide mutational constraint map quantified from variation in 76,156 human genomes [preprint]. https:\/\/doi.org\/10.1101\/2022.03.20.485034 Posted on bioRxiv October 10, 2022","DOI":"10.1101\/2022.03.20.485034"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22187"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.119923"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.06.015"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243105"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.12.005"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.03.010"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv287"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(83)90071-X"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701107"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.037"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63233-3.00019-1"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3453"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2016.02.004"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-072520"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40372"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.012"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn057"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0931-3"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.418889"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.269"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy172"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.smhs.2022.11.005"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22858"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0840-3"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu483"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009242"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1006360"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805361105"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0330-6"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/179559\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:29:38Z","timestamp":1779233378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/179559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6,17]]},"published-print":{"date-parts":[[2024,6,17]]}},"alternative-id":["10.1172\/JCI179559"],"URL":"https:\/\/doi.org\/10.1172\/jci179559","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,17]]},"article-number":"e179559"}}