{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:48:29Z","timestamp":1791625709021,"version":"4.3.4"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n The BORCS5 is an important and critical component of the BLOC\u2010one\u2010related complex (BORC), involved in kinesin\u2010dependent anterograde lysosomal transport. Aberrations in the octameric protein complex encompass lethal neurological manifestations, such as arthrogryposis multiplex congenita, brain malformations and neuropathological evidence of diffuse neuroaxonal dystrophy. Loss\u2010of\u2010function variants in\n BORCS5<\/jats:italic>\n are associated with extremely rapid and progressive neurodegeneration.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Herein, we present a family consisting of a proband with intellectual disability, microcephaly, developmental delay, facial dysmorphism, dystonia, focal\/generalized seizures and speech delay. We performed whole\u2010exome sequencing followed by Sanger sequencing for molecular diagnosis. Further, we performed 3D protein modelling for structural interpretation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Genetic analysis identified a novel stop\u2010gain variant (NM_058169.6, c.262C>T; NP_477517.1, p.(Gln88*)) in\n BORCS5<\/jats:italic>\n , subsequently confirmed by Sanger sequencing. The variant is likely pathogenic (PVS1, PM2, PP3). Protein modelling of the BORCS5; p.(Gln88*) variant showed a distinct conformation compared with the wild\u2010type BORCS5, suggesting a potential role for the unfolded protein response in the pathogenesis of BORCS5.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In summary, our findings exemplify a novel stop\u2010gain variant in\n BORCS5<\/jats:italic>\n associated with diverse pathological manifestations, underscoring the importance of further exploring this gene in patients lacking identifiable disease\u2010causing gene variants.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jdn.70182","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:12:16Z","timestamp":1791011536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel\n BORCS5<\/i>\n Loss\u2010Of\u2010Function Variant in a Patient With a Rare Neurodevelopmental Disorder"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-1230","authenticated-orcid":false,"given":"Arif","family":"Mahmood","sequence":"first","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiStaBiF) University of Campania \u201cLuigi Vanvitelli\u201d Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7740-9427","authenticated-orcid":false,"given":"Abid Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurology Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gohar","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Computer Science Abbottabad University of Science and Technology Havelian Abbottabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazra","family":"Masroof","sequence":"additional","affiliation":[{"name":"Shifa College of Medical Technology Shifa Tameer\u2010e\u2010Millat University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Waqas","sequence":"additional","affiliation":[{"name":"Department of Zoology Emerson University Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-7027","authenticated-orcid":false,"given":"Muhammad","family":"Umair","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Science University of Management and Technology (UMT) Lahore Pakistan"},{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"147","volume-title":"Handbook of Clinical Neurology","author":"Burlina A. 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