biostudies-literatureKucukvardar SIstanbul Teknik ÜniversitesiTürkiye Bilimsel ve Teknolojik Araştırma Kurumudmm052409https://www.ebi.ac.uk/biostudies/studies/S-EPMC12421802biostudies-literatureUnknown18(8)The importance of microtubule stability and microtubule-associated proteins in the etiology of Shwachman-Diamond syndrome (SDS) has been highlighted in recent studies. In one patient with SDS, a novel MAP7D1:c.601C>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 Disease models & mechanismsA novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.PMC12421802121Z610Karabay AKucukvardar SfalseA novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.The importance of microtubule stability and microtubule-associated proteins in the etiology of Shwachman-Diamond syndrome (SDS) has been highlighted in recent studies. In one patient with SDS, a novel MAP7D1:c.601C>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 2025-01-01T00:00:00Z2025 Aug2026-06-02T20:25:57.151Z2026-04-20T03:10:07.942ZS-EPMC124218024085663110.1242/dmm.052409