{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:24:50Z","timestamp":1787743490842,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"state program of the \u00abSirius\u00bb Federal Territory \u00abScientific and technological development of the \u00abSirius\u00bb Federal Territory\u00bb","award":["26-03"],"award-info":[{"award-number":["26-03"]}]},{"name":"Center of Collective Use for Microscopic Analysis of Biological Objects","award":["FWNR-2026-0032"],"award-info":[{"award-number":["FWNR-2026-0032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cohen syndrome, caused by pathogenic variants in VPS13B, is characterized by microcephaly, developmental delay, and progressive retinal degeneration, yet the cellular mechanisms linking VPS13B dysfunction to disease pathology remain incompletely understood. Here, we used CRISPR-Cas9 to delete VPS13B exons 2\u20134 in Phoenix HEK293 cells, generating five independent knockout clones. In all mutant lines, VPS13B disruption caused a marked slowing of cell proliferation due to prolongation of the G1 phase. Immunocytochemistry and transmission electron microscopy revealed that VPS13B mutations causes Golgi apparatus fragmentation, loss of VPS13B Golgi localization, ER lumen dilation with rigid membrane morphology, mitochondrial damage, impaired autophagic maturation, and the appearance of cytoplasmic fibrillary inclusions located close to ER and absent from control cells. RNA-seq analysis identified 27 differentially expressed genes common to all four mutant clones, including downregulation of genes involved in transcriptional regulation, lipid metabolism, and neuronal signaling, alongside upregulation of the stress-response genes CLU and CDKN1A (p21). While our results do not support classical unfolded protein response activation, they are consistent with a model in which lipid bilayer stress and disrupted ER\u2013Golgi trafficking may play a role in the pathophysiology of Cohen syndrome. Together, these findings demonstrate that VPS13B deficiency results in coordinated defects in organelle homeostasis, proteostasis, and cell-cycle progression, providing new dates for understanding Cohen syndrome pathogenesis.<\/jats:p>","DOI":"10.3390\/cells15171535","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:59:23Z","timestamp":1787741963000},"page":"1535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling Cohen Syndrome in Phoenix Cells: VPS13B Loss Causes Organelle Stress, G1\/S Delay, and Fibrillary Inclusion Bodies Formation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3307-8819","authenticated-orcid":false,"given":"Ksenia N.","family":"Morozova","sequence":"first","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina R.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genetic Technologies, Sirius University of Science and Technology, Sirius 354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-499X","authenticated-orcid":false,"given":"Elena V.","family":"Kiseleva","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5152-9914","authenticated-orcid":false,"given":"Alexander V.","family":"Smirnov","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-7906","authenticated-orcid":false,"given":"Elena G.","family":"Pershina","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0226-4213","authenticated-orcid":false,"given":"Inna E.","family":"Pristyazhnyuk","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia"},{"name":"Department of Genetics and Genetic Technologies, Sirius University of Science and Technology, Sirius 354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S0022-3476(73)80493-7","article-title":"A New Syndrome with Hypotonia, Obesity, Mental Deficiency, and Facial, Oral, Ocular, and Limb Anomalies","volume":"83","author":"Cohen","year":"1973","journal-title":"J. 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