{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T06:55:37Z","timestamp":1761375337645,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":2,"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":["82101739"],"award-info":[{"award-number":["82101739"]}],"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;amp; Gen Med"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We identified a novel ABCD1 variant (c.773T&gt;G, p.Leu258Arg, NM_000033.4) in a Chinese pedigree affected by X\u2010linked adrenoleukodystrophy (X\u2010ALD). This missense variant in exon 1 is predicted to be pathogenic and likely constitutes the genetic basis of the disease phenotype in this family.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ABCD1<\/jats:italic>\n                      gene sequencing was performed in the Chinese pedigree. The pathogenicity of identified variants was assessed using computational prediction tools. Subcellular localization studies were conducted, and very\u2010long\u2010chain fatty acid (VLCFA) levels were quantified in patient\u2010derived samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sequencing analysis identified a hemizygous missense variant in the\n                      <jats:italic>ABCD1<\/jats:italic>\n                      gene (c.773T&gt;G; p.Leu258Arg). In silico pathogenicity prediction using SIFT and PolyPhen\u20102 algorithms classified the p.Leu258Arg substitution as deleterious. Functional characterization revealed that the p.Leu258Arg variant impairs the peroxisomal membrane localization of the ABCD1 protein. Consistent with the established role of\n                      <jats:italic>ABCD1<\/jats:italic>\n                      in peroxisomal \u03b2\u2010oxidation, individuals harboring this variant exhibited significantly elevated serum levels of VLCFA. Specifically, the C26:0\/C22:0 ratio was elevated 2.8\u2010fold compared to control values, confirming impaired VLCFA metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In accordance with the \u201cStandards and Guidelines for the Interpretation of Sequence Variants\u201d established by the American College of Medical Genetics and Genomics (ACMG), we assessed the pathogenicity of the novel\n                      <jats:italic>ABCD1<\/jats:italic>\n                      gene variant c.773T&gt;G. This variant meets the following ACMG evidence criteria: PM1 (located within a critical functional domain or mutational hotspot known to lack benign variation); PM2 (absent or observed at very low frequency in population databases e.g., gnomAD, EXAC, 1000 Genomes); PP3 (multiple in silico prediction tools consistently suggest a deleterious effect on the gene or gene product). Integrating this evidence (PM1\u2009+\u2009PM2\u2009+\u2009PP3), the variant is classified as likely pathogenic based on ACMG guidelines. Experimental data from this study further substantiate the pathogenicity of the c.773T&gt;G variant located in exon 1 of the\n                      <jats:italic>ABCD1<\/jats:italic>\n                      gene. This finding broadens the spectrum of known pathogenic mutations in\n                      <jats:italic>ABCD1<\/jats:italic>\n                      associated with X\u2010ALD and provides crucial information for the molecular diagnosis of affected patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70148","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T10:48:42Z","timestamp":1759488522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Missense Variant of the\n                    <i>ABCD1<\/i>\n                    Gene in X\u2010Linked Adrenoleukodystrophy in Chinese Family"],"prefix":"10.1002","volume":"13","author":[{"given":"Hongxia","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Neurology, SSL, Central Hospital of Dongguan City Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University  Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, SSL, Central Hospital of Dongguan City Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University  Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianhong","family":"Liu","sequence":"additional","affiliation":[{"name":"The Center for Precision Medicine, SSL, Central Hospital of Dongguan City Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University  Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory, SSL, Central Hospital of Dongguan City Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University  Dongguan 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