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Hum Mutat. 2018 Feb;39(2):187-192. doi: 10.1002/humu.23368. Epub 2017 Nov 27.

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

Author information

1
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
2
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
3
Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, India.
4
Department of Paediatrics, University of Messina, Messina, Italy.
5
Department of Information and Communications Engineering, University of Murcia University of Murcia, Murcia, Spain.
6
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK.
7
Department of Neuroradiology, Great Ormond Street Hospital for Children, London, UK.

Abstract

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.

KEYWORDS:

DDX59; DEAD-box RNA Helicase; NOTCH signaling; Sonic Hedgehog signaling; leukoencephalopathy; mahe

PMID:
29127725
PMCID:
PMC5814734
DOI:
10.1002/humu.23368
[Indexed for MEDLINE]
Free PMC Article

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