{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:27:54Z","timestamp":1790832474047,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,10,7]],"date-time":"2017-10-07T00:00:00Z","timestamp":1507334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS066927"],"award-info":[{"award-number":["R01NS066927"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Apoptosis\u2010inducing factor mitochondrion\u2010associated\u20101 (<jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1) in mitochondria has captured a great deal of attention due to its well\u2010described function in apoptosis. Mutations in <jats:italic><jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1<\/jats:italic> have resulted in multiple clinical phenotypes, including X\u2010linked Charcot\u2013Marie\u2013Tooth disease type 4. These syndromes usually involve multiple locations within the nervous system and\/or multiple organs. This study describes a novel missense mutation in <jats:italic><jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1<\/jats:italic> and its associated peripheral nerve disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with <jats:italic><jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1<\/jats:italic> mutation were characterized clinically, electrophysiologically, genetically and by magnetic resonance imaging. The fibroblasts were isolated from the patients to study mitochondrial <jats:styled-content style=\"fixed-case\">OXPHOS<\/jats:styled-content> complexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a family with a novel missense mutation (Phe210Leu) in <jats:italic><jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1<\/jats:italic> who developed an isolated late\u2010onset axonal polyneuropathy in which the central nervous system and other organs were spared. Interestingly, this Phe210Leu mutation resulted in abnormal assembly of mitochondrial complex I and <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>, and failed to disrupt <jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1 binding with mitochondrial intermembrane space import and assembly protein 40 (MIA40) in the patients\u2019 cells. Deficiency of either <jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1 or <jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content>40 is known to impair the assembly of mitochondrial complex I and <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content>. However, levels of both <jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content>40 were unchanged.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Phe210Leu mutation in <jats:italic><jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1<\/jats:italic> induces an axonal polyneuropathy that might be contributed by the misassembly of mitochondrial complex I and III. This misassembly appears to be independent of the traditional mechanism via <jats:styled-content style=\"fixed-case\">AIFM<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">MIA<\/jats:styled-content>40 deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13452","type":"journal-article","created":{"date-parts":[[2017,9,9]],"date-time":"2017-09-09T15:06:37Z","timestamp":1504969597000},"page":"1499-1506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["A novel missense mutation in <i><scp>AIFM<\/scp>1<\/i> results in axonal polyneuropathy and misassembly of <scp>OXPHOS<\/scp> complexes"],"prefix":"10.1111","volume":"24","author":[{"given":"B.","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Neurology Center for Human Genetic Research and Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Human Genetic Research and Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Castoro","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Physical Medicine Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Human Genetic Research and Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Dortch","sequence":"additional","affiliation":[{"name":"Department of Radiology Vanderbilt University Medical Center Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Yawn","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Human Genetic Research and Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8431-0812","authenticated-orcid":false,"given":"J.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Human Genetic Research and Vanderbilt Brain Institute Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.04681.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206794"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.170"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00350.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24776"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000919"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.141"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.13452","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.13452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T11:41:38Z","timestamp":1695555698000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.13452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,7]]},"references-count":8,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1111\/ene.13452"],"URL":"https:\/\/doi.org\/10.1111\/ene.13452","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,7]]},"assertion":[{"value":"2017-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}