A loss‐of‐function homozygous mutation in DDX59 implicates a conserved DEAD‐box RNA helicase in nervous system development and function. Issue 2 (27th November 2017)

• Record Type: Journal Article
• Authors: 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 D.; Bettencourt, Conceicao; Mankad, Kshitij; Mukherjee, Ashim; Mutsuddi, Mousumi; Houlden, Henry
• Is Part Of: Human mutation. Volume 39:Issue 2(2018)
• Page Start: 187
• Page End: 192
• Publication Date: 2017-11-27
• Subjects: DEAD‐box RNA Helicase -- DDX59 -- mahe -- leukoencephalopathy -- NOTCH signaling -- Sonic Hedgehog signaling; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23368
• Languages: English
• ISSNs: 1059-7794

Abstract

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. 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. We 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.