{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:38:19Z","timestamp":1792730299758,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":294,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM141050"],"award-info":[{"award-number":["R01GM141050"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    <jats:italic>FITM2<\/jats:italic>\n                    encodes fat storage\u2010inducing transmembrane protein 2 (FIT2), a lipid diphosphatase in the ER that cleaves acyl\u2010CoAs and is crucial for ER homeostasis. In humans, homozygous null mutations in\n                    <jats:italic>FITM2<\/jats:italic>\n                    are associated with a syndrome characterized by deafness and dystonia. Here, we report two families presenting with late childhood\u2010onset, slowly progressive limb spasticity, cerebellar features, and relatively preserved cognition, consistent with a complex hereditary spastic paraplegia (HSP) phenotype in whom exome sequencing revealed compound heterozygosity for\n                    <jats:italic>FITM2<\/jats:italic>\n                    mutations. In each family, the affected probands carry one putative null allele and one G100R missense allele. Functional analyses demonstrated that the G100R allele is hypomorphic, with FIT2 protein levels reduced to 20% of wild type, leading to proportionately decreased enzyme activity. The occurrence of similar HSP disease phenotypes and the same hypomorphic mutation in these families suggests that the G100R mutation and its associated reduced enzyme activity represent a newly recognized clinical manifestation of\n                    <jats:italic>FITM2<\/jats:italic>\n                    mutations, expanding the spectrum of conditions associated with this gene.\n                  <\/jats:p>","DOI":"10.1155\/humu\/5893503","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:03:44Z","timestamp":1792728224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Partial Loss of\n                    <i>FITM2<\/i>\n                    Function Causes Hereditary Spastic Paraplegia"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5753-2687","authenticated-orcid":false,"given":"Ainara","family":"Salazar-Villacorta","sequence":"first","affiliation":[{"name":"Neuromuscular Disorders Department UCL Queen Square Institute of Neurology  London UK"},{"name":"Department of Neurology Great Ormond Street Hospital for Children  London UK  nhs.uk"},{"name":"Developmental Neurosciences Department UCL GOS Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Bond","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism Harvard T.H. Chan School of Public Health  Boston USA  harvard.edu"},{"name":"Department of Cell Biology Harvard Medical School  Boston USA  harvard.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1266-7828","authenticated-orcid":false,"given":"Leehyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Cell Biology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center  New York USA  mskcc.org"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Anagnostopoulou","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Genomedica  Piraeus Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6013-4819","authenticated-orcid":false,"given":"Annarita","family":"Scardamaglia","sequence":"additional","affiliation":[{"name":"Neuromuscular Disorders Department UCL Queen Square Institute of Neurology  London 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uoa.gr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios M.","family":"Vrachnos","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation of the Academy of Athens (BRFAA)  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Loupis","sequence":"additional","affiliation":[{"name":"Hematology Research Lab Clinical Experimental and Translational Research Center Biomedical Research Foundation Academy of Athens  Athens Greece  academyofathens.gr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-0113","authenticated-orcid":false,"given":"Perilikis","family":"Makrythanasis","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Medical School National and Kapodistrian University of Athens  Athens Greece  uoa.gr"},{"name":"Greek Genome Center Biomedical Research Foundation of the Academy of Athens  Athens Greece  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