A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.

ABSTRACT: 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

SUBMITTER: Kucukvardar S 

PROVIDER: S-EPMC12421802 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature