A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function.

Autor: Salpietro V; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Efthymiou S; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Manole A; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Maurya B; Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India., Wiethoff S; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Ashokkumar B; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, India., Cutrupi MC; Department of Paediatrics, University of Messina, Messina, Italy., Dipasquale V; Department of Paediatrics, University of Messina, Messina, Italy., Manti S; Department of Paediatrics, University of Messina, Messina, Italy., Botia JA; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Department of Information and Communications Engineering, University of Murcia University of Murcia, Murcia, Spain., Ryten M; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Vandrovcova J; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Bello OD; Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK., Bettencourt C; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK., Mankad K; Department of Neuroradiology, Great Ormond Street Hospital for Children, London, UK., Mukherjee A; Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India., Mutsuddi M; Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India., Houlden H; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2018 Feb; Vol. 39 (2), pp. 187-192. Date of Electronic Publication: 2017 Nov 27.
DOI: 10.1002/humu.23368
Abstrakt: We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function.
(© 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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