{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:04:02Z","timestamp":1779786242478,"version":"3.53.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NINDS R21 NS098930"],"award-info":[{"award-number":["NINDS R21 NS098930"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      We leveraged consanguinity and population endogamy in a large four generation Turkish family with ET. Examination of clinical features and genetic analysis identified a homozygous\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      missense variant, in a large region of homozygosity, segregating with ET in the family.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The ET family is of Turkish origin. The proband and relatives were evaluated at Ankara University Medical School and Bilkent University (Ankara, Turkey). A second evaluation of the clinical and videotape data was performed at Yale University. A total of 6 individuals from the family were clinically assessed. Whole genome sequencing and autozygosity mapping was performed in affected and unaffected family members. Transient transfection of HEK293T cells was performed to assess pathogenicity of the\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      missense variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 4 family members were diagnosed with ET; two individuals also had a diagnosis of Parkinson\u2019s Disease (PD). We identified a missense variant in\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      , p.Ser166Leu, located within a 7.7\u202fMb region of homozygosity (ROH) (Chr12: 46595701\u201354,330,441), which was observed in all analyzed affected family members. Unlike wildtype\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      which localizes to nuclear speckles in the nuclear compartment, when mutant\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      was expressed in HEK293T cells we observed enrichment and localization to the nuclear membrane.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      p.Ser166Leu variant is located within a conserved region of the WW protein domain.\n                      <jats:italic>In Silico<\/jats:italic>\n                      pathogenicity and functional studies predict that the missense variant alters the function of\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      .\n                      <jats:italic>PRPF40B<\/jats:italic>\n                      has previously been implicated in the pathogenesis of neurological disorders, including Huntington\u2019s disease and Rett syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1796664","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:17:59Z","timestamp":1779783479000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A homozygous missense variant, p.Ser166Leu in the PRPF40B gene, in a 7.7\u202fMb region of homozygosity in a consanguineous Turkish family with essential tremor"],"prefix":"10.3389","volume":"17","author":[{"given":"Onur Emre","family":"Onat","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Bilkent University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Sonti","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University","place":["New York, NY, United States"]},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Robakis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse B.","family":"Tekinay","sequence":"additional","affiliation":[{"name":"Institute of Materials Science and Nanotechnology, Bilkent University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cenk","family":"Akbostanci","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Ankara University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Nazli","family":"Durmaz Celik","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Osmangazi University","place":["Eskisehir, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayfun","family":"Ozcelik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Bilkent University","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine N.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1056\/NEJMcp010928","article-title":"Clinical practice. 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