{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:22:09Z","timestamp":1787026929973,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>As a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been identified to cause AMN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied clinical evaluation, laboratory tests, and neuroimaging on three patients with progressive spastic paraparesis. In genetic analysis, we investigated ABCD1 gene mutations by whole-exome sequencing and Sanger sequencing. Bioinformatics tools were used to predict the effects of identified ABCD1 mutations on the protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All three patients were men with adult-onset disease, mainly characterized by progressive spastic paraparesis. Among them, two patients had peripheral neuropathy and one patient had signs of adrenal insufficiency. All three patients showed cerebral involvement on brain MRI, while two patients were found with diffuse cord atrophy on spinal MRI. High-VLCFA levels in plasma, as well as C24:0\/C22:0 and C26:0\/C22:0 ratios, were found in all three patients. In addition, three different ABCD1 mutations were identified in three unrelated Chinese families, including one known mutation (c.1415_1416delAG) and two novel mutations (c.217C&amp;gt;T and c.160_170delACGCAGGAGGC). Based on the clinical assessment, radiographic, biochemical, and genetic testing, the final diagnosis was AMN in these patients with spastic paraparesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reported three patients with AMN and identified two novel mutations in the ABCD1 in the Chinese population. Our finding emphasized that X-ALD is an important cause of adult-onset spastic paraplegia. Thus, neuroimaging, VLCFA testing, and especially the detection of the ABCD1 gene have important implications for the etiological diagnosis of adult patients with spastic paraplegia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2023.1126729","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T12:24:53Z","timestamp":1678105493000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel mutations in the ABCD1 gene caused adrenomyeloneuropathy in the Chinese population"],"prefix":"10.3389","volume":"14","author":[{"given":"Raoli","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoen","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangyu","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3131","DOI":"10.1001\/jama.294.24.3131","article-title":"Adrenoleukodystrophy: new approaches to neurodegenerative disease","volume":"294","author":"Moser","year":"2005","journal-title":"JAMA."},{"key":"B2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1750-1172-7-51","article-title":"X-linked adrenoleukodystrophy","volume":"7","author":"Engelen","year":"2012","journal-title":"Orphanet J Rare Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/1531-8249(20010201)49:2<186::aid-ana38>3.0.co;2-r","article-title":"Evolution of phenotypes in adult male patients with X-linked adrenoleukodystrophy","volume":"49","author":"van Geel","year":"2001","journal-title":"Ann Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1212\/WNL.0000000000000415","article-title":"Small nerve fiber involvement is frequent in X-linked adrenoleukodystrophy","volume":"82","author":"Horn","year":"2014","journal-title":"Neurology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat Protoc."},{"key":"B6","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods."},{"key":"B7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations","volume":"7","author":"Schwarz","year":"2010","journal-title":"Nat Methods."},{"key":"B8","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines","volume":"100","author":"Li","year":"2017","journal-title":"Am J Hum Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1093\/brain\/awy127","article-title":"Impaired plasticity of macrophages in X-linked adrenoleukodystrophy","volume":"141","author":"Weinhofer","year":"2018","journal-title":"Brain."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1212\/wnl.27.12.1107","article-title":"Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. 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