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

Autores
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
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Salpietro, Vincenzo. University College London; Estados Unidos
Fil: Efthymiou, Stephanie. University College London; Estados Unidos
Fil: Manole, Andreea. University College London; Estados Unidos
Fil: Maurya, Bhawana. Banaras Hindu University; India
Fil: Wiethoff, Sarah. University College London; Estados Unidos
Fil: Ashokkumar, Balasubramaniem. University College London; Estados Unidos
Fil: Cutrupi, Maria Concetta. University of Messina; Italia
Fil: Dipasquale, Valeria. University of Messina; Italia
Fil: Manti, Sara. University of Messina; Italia
Fil: Botia, Juan A.. University College London; Estados Unidos
Fil: Ryten, Mina. University College London; Estados Unidos
Fil: Vandrovcova, Jana. University College London; Estados Unidos
Fil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Bettencourt, Conceicao. University College London; Estados Unidos
Fil: Mankad, Kshitij. Great Ormond Street Hospital for Children; Reino Unido
Fil: Mukherjee, Ashim. Banaras Hindu University; India
Fil: Mutsuddi, Mousumi. Banaras Hindu University; India
Fil: Houlden, Henry. University College London; Estados Unidos
Materia
DDX59
DEAD-BOX RNA HELICASE
LEUKOENCEPHALOPATHY
MAHE
NOTCH SIGNALING
SONIC HEDGEHOG SIGNALING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/160097
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/160097
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and functionSalpietro, VincenzoEfthymiou, StephanieManole, AndreeaMaurya, BhawanaWiethoff, SarahAshokkumar, BalasubramaniemCutrupi, Maria ConcettaDipasquale, ValeriaManti, SaraBotia, Juan A.Ryten, MinaVandrovcova, JanaBello, Oscar DanielBettencourt, ConceicaoMankad, KshitijMukherjee, AshimMutsuddi, MousumiHoulden, HenryDDX59DEAD-BOX RNA HELICASELEUKOENCEPHALOPATHYMAHENOTCH SIGNALINGSONIC HEDGEHOG SIGNALINGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We 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.Fil: Salpietro, Vincenzo. University College London; Estados UnidosFil: Efthymiou, Stephanie. University College London; Estados UnidosFil: Manole, Andreea. University College London; Estados UnidosFil: Maurya, Bhawana. Banaras Hindu University; IndiaFil: Wiethoff, Sarah. University College London; Estados UnidosFil: Ashokkumar, Balasubramaniem. University College London; Estados UnidosFil: Cutrupi, Maria Concetta. University of Messina; ItaliaFil: Dipasquale, Valeria. University of Messina; ItaliaFil: Manti, Sara. University of Messina; ItaliaFil: Botia, Juan A.. University College London; Estados UnidosFil: Ryten, Mina. University College London; Estados UnidosFil: Vandrovcova, Jana. University College London; Estados UnidosFil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Bettencourt, Conceicao. University College London; Estados UnidosFil: Mankad, Kshitij. Great Ormond Street Hospital for Children; Reino UnidoFil: Mukherjee, Ashim. Banaras Hindu University; IndiaFil: Mutsuddi, Mousumi. Banaras Hindu University; IndiaFil: Houlden, Henry. University College London; Estados UnidosWiley-liss, div John Wiley & Sons Inc.2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/160097Salpietro, 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; 187-1921059-7794CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/humu.23368info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/humu.23368info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:22Zoai:ri.conicet.gov.ar:11336/160097instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:41:23.093CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
title A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
spellingShingle A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
Salpietro, Vincenzo
DDX59
DEAD-BOX RNA HELICASE
LEUKOENCEPHALOPATHY
MAHE
NOTCH SIGNALING
SONIC HEDGEHOG SIGNALING
title_short A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
title_full A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
title_fullStr A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
title_full_unstemmed A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
title_sort A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
dc.creator.none.fl_str_mv 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
author Salpietro, Vincenzo
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DDX59
DEAD-BOX RNA HELICASE
LEUKOENCEPHALOPATHY
MAHE
NOTCH SIGNALING
SONIC HEDGEHOG SIGNALING
topic DDX59
DEAD-BOX RNA HELICASE
LEUKOENCEPHALOPATHY
MAHE
NOTCH SIGNALING
SONIC HEDGEHOG SIGNALING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Salpietro, Vincenzo. University College London; Estados Unidos
Fil: Efthymiou, Stephanie. University College London; Estados Unidos
Fil: Manole, Andreea. University College London; Estados Unidos
Fil: Maurya, Bhawana. Banaras Hindu University; India
Fil: Wiethoff, Sarah. University College London; Estados Unidos
Fil: Ashokkumar, Balasubramaniem. University College London; Estados Unidos
Fil: Cutrupi, Maria Concetta. University of Messina; Italia
Fil: Dipasquale, Valeria. University of Messina; Italia
Fil: Manti, Sara. University of Messina; Italia
Fil: Botia, Juan A.. University College London; Estados Unidos
Fil: Ryten, Mina. University College London; Estados Unidos
Fil: Vandrovcova, Jana. University College London; Estados Unidos
Fil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Bettencourt, Conceicao. University College London; Estados Unidos
Fil: Mankad, Kshitij. Great Ormond Street Hospital for Children; Reino Unido
Fil: Mukherjee, Ashim. Banaras Hindu University; India
Fil: Mutsuddi, Mousumi. Banaras Hindu University; India
Fil: Houlden, Henry. University College London; Estados Unidos
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/160097
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
url http://hdl.handle.net/11336/160097
identifier_str_mv 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
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/humu.23368
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/humu.23368
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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