{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:47:34Z","timestamp":1788292054868,"version":"build-2803163510"},"reference-count":33,"publisher":"The Company of Biologists","issue":"8","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","award":["121Z610"],"award-info":[{"award-number":["121Z610"]}]},{"DOI":"10.13039\/501100007504","name":"Istanbul Teknik \u00dcniversitesi","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007504","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The importance of microtubule stability and microtubule-associated proteins in the etiology of Shwachman\u2212Diamond syndrome (SDS) has been highlighted in recent studies. In one patient with SDS, a novel MAP7D1:c.601C&amp;gt;T, p.R201W variant has been identified. In this study, the causality of this variant in the pathogenesis of SDS was investigated. Mutation in the microtubule-binding domain of MAP7D1 caused disruption of its interaction with microtubules. SDS fibroblasts exhibited a decreased cell size with reduced microtubule density, and mitotic defects, including multipolar or bipolar unstable spindles, lagging chromosomes, and shortened inter-centrosomal distance. Additionally, ribosomal protein S14 (RPS14) accumulated within incorrectly dividing SDS fibroblasts. To further evaluate whether these abnormalities are directly attributable to the MAP7D1 mutation, mitotic processes were investigated through genetic manipulations of MAP7D1 in T98G glioblastoma and HEK293T embryonic kidney cell lines. Consistent with data from SDS fibroblasts, similar phenotypes were detected upon overexpression of mutant MAP7D1 and depletion of MAP7D1. Our findings revealed that the MAP7D1 mutation acts as a loss-of-function mutation and contributes to SDS pathogenesis by disrupting microtubule dynamics and ribosomal protein regulation, identifying MAP7D1 as a gene with substantial impact for SDS.<\/jats:p>","DOI":"10.1242\/dmm.052409","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T13:21:52Z","timestamp":1756214512000},"source":"Crossref","is-referenced-by-count":2,"title":["A novel <i>MAP7D1<\/i> mutation causes mitotic defects and RPS14 accumulation in Shwachman\u2212Diamond syndrome patient cells"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3164-6598","authenticated-orcid":false,"given":"Seren","family":"Kucukvardar","sequence":"first","affiliation":[{"name":"Graduate School, Istanbul Technical University 1 Molecular Biology-Genetics and Biotechnology , , Maslak 34469, Istanbul,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-5349","authenticated-orcid":false,"given":"Arzu","family":"Karabay","sequence":"additional","affiliation":[{"name":"Graduate School, Istanbul Technical University 1 Molecular Biology-Genetics and Biotechnology , , Maslak 34469, Istanbul,","place":["Turkey"]},{"name":"Istanbul Technical University 2 Department of Molecular Biology and Genetics , , Maslak 34469, Istanbul,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"2025082903011043100_DMM052409C1","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1172\/JCI33764","article-title":"Mitotic spindle destabilization and genomic instability in Shwachman\u2212Diamond syndrome","volume":"118","author":"Austin","year":"2008","journal-title":"J. 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