dc.contributor
Institut Català de la Salut
dc.contributor
[Dharmadhikari AV] Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA. Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Abad MA] Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom. [Khan S] Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA. Departments of Pediatrics and Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Human Molecular Genetics Lab, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE-C), Faisalabad, Pakistan. Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, Pakistan. [Maroofian R] Department of Neuromuscular Diseases, University College London, Queen Square, Institute of Neurology, London, UK. [Sands TT] Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. [Ullah F] Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA. Departments of Pediatrics and Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. [Perez-Duenas B] Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Department of Paediatrics, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Cazurro-Gutierrez A] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. [Verdura E] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Molecular Biology CORE, Biomedical Diagnostic Center (CDB), Hospital Clínic de Barcelona, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Dharmadhikari, Avinash
dc.contributor.author
Abad, Maria Alba
dc.contributor.author
Khan, Sheraz
dc.contributor.author
Maroofian, Reza
dc.contributor.author
Sands, Tristan T.
dc.contributor.author
Ullah, Farid
dc.contributor.author
Cazurro Gutiérrez, Ana Laura
dc.contributor.author
Verdura, Edgard
dc.contributor.author
PEREZ DUEÑAS, BELEN
dc.date.accessioned
2025-05-03T13:41:05Z
dc.date.available
2025-05-03T13:41:05Z
dc.date.issued
2025-03-31T11:46:39Z
dc.date.issued
2025-03-31T11:46:39Z
dc.date.issued
2025-02-17
dc.identifier
Dharmadhikari AV, Abad MA, Khan S, Maroofian R, Sands TT, Ullah F, et al. RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS. Nat Commun. 2025 Feb 17;16:1703.
dc.identifier
http://hdl.handle.net/11351/12853
dc.identifier
10.1038/s41467-025-56876-w
dc.identifier
001424373700016
dc.identifier.uri
http://hdl.handle.net/11351/12853
dc.description.abstract
RNA methyltransferase; Mitotic spindle; Neurodevelopmental disorder
dc.description.abstract
ARN metiltransferasa; Huso mitótico; Trastorno del desarrollo neurológico
dc.description.abstract
ARN metiltransferasa; Fus mitòtic; Trastorn del desenvolupament neurològic
dc.description.abstract
SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays from 21 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants show reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicate that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 reveals that most disease-associated missense variants are located within the catalytic domain. Additionally, SPOUT1/CENP-32 recurrent missense variants show reduced methyltransferase activity in vitro and compromised centrosome tethering to the spindle poles in human cells. Thus, SPOUT1/CENP-32 pathogenic variants cause an autosomal recessive neurodevelopmental disorder: SpADMiSS (SPOUT1 Associated Development delay Microcephaly Seizures Short stature) underpinned by mitotic spindle organization defects and consequent chromosome segregation errors.
dc.format
application/pdf
dc.publisher
Nature Portfolio
dc.relation
Nature Communications;16
dc.relation
https://doi.org/10.1038/s41467-025-56876-w
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Malalties mentals
dc.subject
Neurobiologia del desenvolupament
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Anomalies cromosòmiques
dc.subject
PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurodevelopmental Disorders
dc.subject
ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Fishes::Cypriniformes::Cyprinidae::Zebrafish
dc.subject
ANATOMY::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Spindle Apparatus
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Mutation, Missense
dc.subject
PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del desarrollo neurológico
dc.subject
ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::peces::Cipriniformes::Cyprinidae::pez cebra
dc.subject
ANATOMÍA::células::estructuras celulares::espacio intracelular::citoplasma::estructuras citoplasmáticas::citoesqueleto::huso acromático
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de sentido erróneo
dc.title
RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
