Mutations in Citron Kinase Cause Recessive Microlissencephaly with Multinucleated Neurons - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue American Journal of Human Genetics Année : 2016

Mutations in Citron Kinase Cause Recessive Microlissencephaly with Multinucleated Neurons

Sylvie Joriot
  • Fonction : Auteur
  • PersonId : 925168

Résumé

Primary microcephaly is a neurodevelopmental disorder that is caused by a reduction in brain size as a result of defects in the proliferation of neural progenitor cells during development. Mutations in genes encoding proteins that localize to the mitotic spindle and centrosomes have been implicated in the pathogenicity of primary microcephaly. In contrast, the contractile ring and midbody required for cytokinesis, the final stage of mitosis, have not previously been implicated by human genetics in the molecular mechanisms of this phenotype. Citron kinase (CIT) is a multi-domain protein that localizes to the cleavage furrow and midbody of mitotic cells, where it is required for the completion of cytokinesis. Rodent models of Cit deficiency highlighted the role of this gene in neurogenesis and microcephaly over a decade ago. Here, we identify recessively inherited pathogenic variants in CIT as the genetic basis of severe microcephaly and neonatal death. We present postmortem data showing that CIT is critical to building a normally sized human brain. Consistent with cytokinesis defects attributed to CIT, multinucleated neurons were observed throughout the cerebral cortex and cerebellum of an affected proband, expanding our understanding of mechanisms attributed to primary microcephaly.
Fichier principal
Vignette du fichier
Harding,AJHG 2016_final version before copyright.pdf (1010.68 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02324787 , version 1 (08-06-2020)

Identifiants

Citer

Brian N. Harding, Amanda Moccia, Séverine Drunat, Omar Soukarieh, Hélène Tubeuf, et al.. Mutations in Citron Kinase Cause Recessive Microlissencephaly with Multinucleated Neurons. American Journal of Human Genetics, 2016, 99 (2), pp.511-520. ⟨10.1016/j.ajhg.2016.07.003⟩. ⟨hal-02324787⟩
68 Consultations
78 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More