{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:51:44Z","timestamp":1777945904229,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112\u20102314\u2010B\u2010075\u2010034\u2010MY3"],"award-info":[{"award-number":["112\u20102314\u2010B\u2010075\u2010034\u2010MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112\u20102320\u2010B\u2010005\u2010012"],"award-info":[{"award-number":["112\u20102320\u2010B\u2010005\u2010012"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n TFG<\/jats:italic>\n mutations have previously been implicated in autosomal recessive hereditary spastic paraplegia (HSP), also known as SPG57. This study aimed to investigate the clinical and molecular features of\n TFG<\/jats:italic>\n mutations in a Taiwanese HSP cohort.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Genetic analysis of\n TFG<\/jats:italic>\n was conducted in 242 unrelated Taiwanese HSP patients using a targeted resequencing panel covering the entire coding regions of\n TFG<\/jats:italic>\n . Functional assays were performed using an\n in vitro<\/jats:italic>\n cell model to assess the impact of\n TFG<\/jats:italic>\n variants on protein function. Additionally, other representative TFG mutant proteins were examined to understand the broader implications of\n TFG<\/jats:italic>\n mutations in HSP.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study identified a novel homozygous\n TFG<\/jats:italic>\n c.177A>C (p.(Lys59Asn)) variant in a family with adolescent\u2010onset, pure form HSP. Functional analysis revealed that the Lys59Asn TFG variant, similar to other HSP\u2010associated TFG mutants, exhibited a low affinity between TFG monomers and abnormal assembly of TFG homo\u2010oligomers. These structural alterations led to aberrant intracellular distribution, compromising TFG's protein secretion function and resulting in decreased cellular viability.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n These findings confirm that the homozygous\n TFG<\/jats:italic>\n c.177A>C (p.(Lys59Asn)) variant is a novel cause of SPG57. The study expands our understanding of the clinical and mutational spectrum of\n TFG<\/jats:italic>\n \u2010associated diseases, highlighting the functional defects associated with this specific\n TFG<\/jats:italic>\n variant. Overall, this research contributes to the broader comprehension of the genetic and molecular mechanisms underlying HSP.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acn3.52113","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T01:39:37Z","timestamp":1717551577000},"page":"1909-1920","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of a novel\n \n TFG<\/i>\n <\/scp>\n variant causing autosomal recessive pure hereditary spastic paraplegia"],"prefix":"10.1002","volume":"11","author":[{"given":"Cheng\u2010Tsung","family":"Hsiao","sequence":"first","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine Taipei 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