info:eu-repo/semantics/article
A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
Fecha
2018-02Registro en:
Salpietro, Vincenzo; Efthymiou, Stephanie; Manole, Andreea; Maurya, Bhawana; Wiethoff, Sarah; et al.; A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function; Wiley-liss, div John Wiley & Sons Inc.; Human Mutation; 39; 2; 2-2018; 187-192
1059-7794
CONICET Digital
CONICET
Autor
Salpietro, Vincenzo
Efthymiou, Stephanie
Manole, Andreea
Maurya, Bhawana
Wiethoff, Sarah
Ashokkumar, Balasubramaniem
Cutrupi, Maria Concetta
Dipasquale, Valeria
Manti, Sara
Botia, Juan A.
Ryten, Mina
Vandrovcova, Jana
Bello, Oscar Daniel
Bettencourt, Conceicao
Mankad, Kshitij
Mukherjee, Ashim
Mutsuddi, Mousumi
Houlden, Henry
Resumen
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.