{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:23:22Z","timestamp":1791581002408,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671040"],"award-info":[{"award-number":["81671040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in the mitochondrial alanyl\u2010transfer (t)<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> synthetase 2 <jats:italic>(<jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>,<jats:styled-content style=\"fixed-case\">OMIM<\/jats:styled-content>:612035) have been linked to leukoencephalopathy recently. Till now, there have been 19 cases reported so far. However, the clinical and genetic characteristics of this disease are not fully understood. We reported an adult\u2010onset male leukoencephalopathy patient related to novel <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic> gene mutations and reviewed all previous cases regarding the clinical and genetic features of <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic> leukoencephalopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The spectrum of clinical symptoms and the genetic analysis of the presented patient were identified and investigated. Besides this case, we assessed previously reported cases with <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic> gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we present a 30\u2010year\u2010old man with progressive motor deficits in the right lower limb and severe cerebellar ataxia for one year. <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> revealed extensive white matter lesions in periventricular regions and along the corticospinal tract. Genetic analysis revealed two new heterogeneous missense mutations in <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>: c.179C&gt;A and c.1703_1704del. We described the ragged red fiber (<jats:styled-content style=\"fixed-case\">RRF<\/jats:styled-content>) for the first time, suggesting that <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>\u2010related leukoencephalopathy be a new variant of mitochondrial encephalomyopathy. Gradual improvement in motor function was observed with intravenous coenzyme complex treatment. We also summarized our case and all previously reported cases to provide an overview of <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>\u2010related late\u2010onset leukoencephalopathy. Then, we compared clinical and neuroimaging features of <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>\u2010related leukoencephalopathy with three other frequently diagnosed types of adult\u2010onset leukoencephalopathy to provide insight into diagnostic strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The characteristic <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> abnormalities and clinical symptoms described here may help to distinguish <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>\u2010related leukoencephalopathy from other adult\u2010onset leukoencephalopathies. The combination of encephalopathy and myopathy strongly suggest that <jats:italic><jats:styled-content style=\"fixed-case\">AARS<\/jats:styled-content>2<\/jats:italic>\u2010related leukoencephalopathy is a new variant of mitochondrial encephalomyopathy. The response to coenzyme complex will shed light on future therapy investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.582","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T01:31:44Z","timestamp":1548984704000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["<i><scp>AARS<\/scp>2<\/i> leukoencephalopathy: A new variant of mitochondrial encephalomyopathy"],"prefix":"10.1002","volume":"7","author":[{"given":"Yi","family":"Tang","sequence":"first","affiliation":[{"name":"Innovation Center for Neurological Disorders Department of Neurology Xuan Wu Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-2061","authenticated-orcid":false,"given":"Qi","family":"Qin","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders Department of Neurology Xuan Wu Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xing","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders Department of Neurology Xuan Wu Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Guo","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders Department of Neurology Xuan Wu Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Di","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders Department of Neurology Xuan Wu Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Jia","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders Department of Neurology Xuan Wu Hospital Capital Medical University Beijing China"},{"name":"Center of Alzheimer's Disease Beijing Institute for Brain Disorders Beijing Key Laboratory of Geriatric Cognitive Disorders Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000033795.17156.00"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2004.07.036"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003310"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000497"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/787956"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-018-0446-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00021"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.04.006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174343"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.64"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/331717a0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.62.9.1464"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000135"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13245"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx045"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.2229"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70116-2"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.1.93"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23277"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2017.1350723"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1306380"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2013"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000343049.00540.c8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199810000-00012"},{"key":"e_1_2_8_26_1","first-page":"238","article-title":"The value of the muscle biopsy (a Review of 2300 Confirmed Cases)","volume":"27","author":"Shy G. 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