{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:50:39Z","timestamp":1768283439492,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T00:00:00Z","timestamp":1636848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-D-110038; TSGH-D-110039"],"award-info":[{"award-number":["TSGH-D-110038; TSGH-D-110039"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Affairs Bureau, Ministry of National Defense","award":["MND-MAB-110-053"],"award-info":[{"award-number":["MND-MAB-110-053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Cockayne syndrome (CS) is a rare form of dwarfism that is characterized by progressive premature aging. CS is typically caused by mutations in the excision repair cross-complementing protein group 6 (ERCC6) gene that encodes the CS group B (CSB) protein. Using whole exome sequencing, we recently identified a novel homozygous missense mutation (Leu536Trp) in CSB in a Taiwanese boy with CS. Since the current database (Varsome) interprets this variant as likely pathogenic, we utilized a bioinformatic tool to investigate the impact of Leu536Trp as well as two other variants (Arg453Ter, Asp532Gly) in similar articles on the CSB protein structure stability. Methods: We used iterative threading assembly refinement (I-TASSER) to generate a predictive 3D structure of CSB. We calculated the change of mutation energy after residues substitution on the protein stability using I-TASSER as well as the artificial intelligence program Alphafold. Results: The Asp532Gly variant destabilized both modeled structures, while the Leu536Trp variant showed no effect on I-TASSER\u2019s model but destabilized the Alphafold\u2019s modeled structure. Conclusions: We propose here the first case of CS associated with a novel homozygous missense mutation (Leu536Trp) in CSB. Furthermore, we suggest that the Asp532Gly and Leu536Trp variants are both pathogenic after bioinformatic analysis of protein stability.<\/jats:p>","DOI":"10.3390\/life11111230","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:51:53Z","timestamp":1636923113000},"page":"1230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Whole Exome Sequencing Identifies a Novel Homozygous Missense Mutation in the CSB Protein-Encoding ERCC6 Gene in a Taiwanese Boy with Cockayne Syndrome"],"prefix":"10.3390","volume":"11","author":[{"given":"Ching-Ming","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Department of Pediatrics, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay-How","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwei-Jen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Pang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ping","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Sin","family":"Hsu","sequence":"additional","affiliation":[{"name":"Genomics Center for Clinical and Biotechnological Applications of Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-8906","authenticated-orcid":false,"given":"G. W. Gant","family":"Luxton","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-0890","authenticated-orcid":false,"given":"Chih-Fen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.arr.2016.08.002","article-title":"Cockayne syndrome: Clinical features, model systems and pathways","volume":"33","author":"Karikkineth","year":"2017","journal-title":"Ageing Res. 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