{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:26:18Z","timestamp":1767086778689,"version":"3.48.0"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":17,"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":["82230062"],"award-info":[{"award-number":["82230062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aims to expand the clinical and genetic spectrum of Krabbe disease (KD) in Chinese adult patients and to improve diagnosis and understanding of its phenotypic diversity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients clinically suspected of leukodystrophy were recruited between 2015 and 2025. Clinical features were collected, and whole\u2010exome sequencing (WES) was performed to identify potential variants. The pathogenicity of detected variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Functional assays assessing protein expression, processing, secretion, subcellular localization, and enzymatic activity were conducted to further validate variant pathogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fourteen unrelated patients were genetically diagnosed with KD, and their genetic and clinical features were summarized. Eleven variants in\n                      <jats:italic>GALC<\/jats:italic>\n                      were identified, including a novel missense variant c.1019C&gt;T (p.P340L) which is not reported in the Human Gene Mutation Database (HGMD). Unlike most adult patients who typically present with spastic paraplegia, the patient carrying this variant exhibited initial symptoms of peripheral neuropathy. Functional experiments demonstrated that the variant led to impaired protein processing and localization, as well as reduced GALC enzymatic activity. Other variants including p.D56H, p.L377X, p.L441X, and p.L634S also affected GALC functions to varying degrees.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study enhances the genotypic and phenotypic characterization of KD in China, aiding in differential diagnosis and genetic counseling. Functional data reinforce the pathogenicity of identified variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70708","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T06:44:17Z","timestamp":1766126657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease"],"prefix":"10.1002","volume":"31","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation  Hangzhou China"},{"name":"Nanhu Brain\u2010Computer Interface Institute  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Fen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation  Hangzhou China"},{"name":"Department of Neurology, Lishui Hospital Zhejiang University School of Medicine  Lishui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan\u2010Juan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-572X","authenticated-orcid":false,"given":"Zhi\u2010Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation  Hangzhou China"},{"name":"Nanhu Brain\u2010Computer Interface Institute  Hangzhou China"},{"name":"MOE Frontier Science Center for Brain Science and Brain\u2010Machine Integration, School of Brain Science and Brain Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.11.1841"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110315"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6383-09.2010"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23873"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738211027717"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.10.001"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01489-3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.52078"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000112163"},{"issue":"2","key":"e_1_2_12_11_1","first-page":"316","article-title":"Globoid Cell Leukodystrophy: Distinguishing Early\u2010Onset From Late\u2010Onset Disease Using a Brain MR Imaging Scoring Method","volume":"20","author":"Loes D. 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