A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects

Autores
Favaro, Francine P.; Alvizi, Lucas; Zechi Ceide, Roseli M.; Bertola, Debora; Felix, Temis M.; de Souza, Josiane; Raskin, Salmo; Twigg, Stephen R. F.; Weiner, Andrea Maria Julia; Armas, Pablo; Margarit, Ezequiel; Calcaterra, Nora Beatriz; Andersen, Gregers R.; McGowan, Simon J.; Wilkie, Andrew O. M.; Richieri Costa, Antonio; de Almeida, Maria L. G.; Passos Bueno, Maria Rita
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 50 untranslated region (50 UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPSaffected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis.
Fil: Favaro, Francine P.. Universidade de Sao Paulo; Brasil
Fil: Alvizi, Lucas. Universidade de Sao Paulo; Brasil
Fil: Zechi Ceide, Roseli M.. Universidade de Sao Paulo; Brasil
Fil: Bertola, Debora. Universidade de Sao Paulo; Brasil
Fil: Felix, Temis M.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: de Souza, Josiane. Centro de Atendimento Integral ao Fissurado La´bio Palatal; Brasil
Fil: Raskin, Salmo. Pontifícia Universidade Católica do Paraná. Núcleo de Investigação Molecular Avançada. Centro de Ciências Biológicas e da Saúde; Brasil
Fil: Twigg, Stephen R. F.. University of Oxford; Reino Unido
Fil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Margarit, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Andersen, Gregers R.. University Aarhus; Dinamarca
Fil: McGowan, Simon J.. University of Oxford; Reino Unido
Fil: Wilkie, Andrew O. M.. University of Oxford; Reino Unido
Fil: Richieri Costa, Antonio. Universidade de Sao Paulo; Brasil
Fil: de Almeida, Maria L. G.. Universidade de Sao Paulo; Brasil
Fil: Passos Bueno, Maria Rita. Universidade de Sao Paulo; Brasil
Materia
Noncoding Expansion
Richieri-Costa-Pereira Syndrome
Craniofacial Disorder
Limb Defects
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8819
Acceder
id CONICETDig_b749743ac60bf388811bb9316e74d02d
oai_identifier_str oai:ri.conicet.gov.ar:11336/8819
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb DefectsFavaro, Francine P.Alvizi, LucasZechi Ceide, Roseli M.Bertola, DeboraFelix, Temis M.de Souza, JosianeRaskin, SalmoTwigg, Stephen R. F.Weiner, Andrea Maria JuliaArmas, PabloMargarit, EzequielCalcaterra, Nora BeatrizAndersen, Gregers R.McGowan, Simon J.Wilkie, Andrew O. M.Richieri Costa, Antoniode Almeida, Maria L. G.Passos Bueno, Maria RitaNoncoding ExpansionRichieri-Costa-Pereira SyndromeCraniofacial DisorderLimb Defectshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 50 untranslated region (50 UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPSaffected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis.Fil: Favaro, Francine P.. Universidade de Sao Paulo; BrasilFil: Alvizi, Lucas. Universidade de Sao Paulo; BrasilFil: Zechi Ceide, Roseli M.. Universidade de Sao Paulo; BrasilFil: Bertola, Debora. Universidade de Sao Paulo; BrasilFil: Felix, Temis M.. Universidade Federal do Rio Grande do Sul; BrasilFil: de Souza, Josiane. Centro de Atendimento Integral ao Fissurado La´bio Palatal; BrasilFil: Raskin, Salmo. Pontifícia Universidade Católica do Paraná. Núcleo de Investigação Molecular Avançada. Centro de Ciências Biológicas e da Saúde; BrasilFil: Twigg, Stephen R. F.. University of Oxford; Reino UnidoFil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Margarit, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Andersen, Gregers R.. University Aarhus; DinamarcaFil: McGowan, Simon J.. University of Oxford; Reino UnidoFil: Wilkie, Andrew O. M.. University of Oxford; Reino UnidoFil: Richieri Costa, Antonio. Universidade de Sao Paulo; BrasilFil: de Almeida, Maria L. G.. Universidade de Sao Paulo; BrasilFil: Passos Bueno, Maria Rita. Universidade de Sao Paulo; BrasilCell Press2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8819Favaro, Francine P.; Alvizi, Lucas; Zechi Ceide, Roseli M.; Bertola, Debora; Felix, Temis M.; et al.; A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects; Cell Press; American Journal Of Human Genetics; 94; 1; 1-2014; 120-1280002-9297enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0002929713005351info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajhg.2013.11.020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:10Zoai:ri.conicet.gov.ar:11336/8819instacron: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:34982025-09-03 10:09:11.103CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
title A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
spellingShingle A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
Favaro, Francine P.
Noncoding Expansion
Richieri-Costa-Pereira Syndrome
Craniofacial Disorder
Limb Defects
title_short A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
title_full A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
title_fullStr A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
title_full_unstemmed A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
title_sort A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects
dc.creator.none.fl_str_mv Favaro, Francine P.
Alvizi, Lucas
Zechi Ceide, Roseli M.
Bertola, Debora
Felix, Temis M.
de Souza, Josiane
Raskin, Salmo
Twigg, Stephen R. F.
Weiner, Andrea Maria Julia
Armas, Pablo
Margarit, Ezequiel
Calcaterra, Nora Beatriz
Andersen, Gregers R.
McGowan, Simon J.
Wilkie, Andrew O. M.
Richieri Costa, Antonio
de Almeida, Maria L. G.
Passos Bueno, Maria Rita
author Favaro, Francine P.
author_facet Favaro, Francine P.
Alvizi, Lucas
Zechi Ceide, Roseli M.
Bertola, Debora
Felix, Temis M.
de Souza, Josiane
Raskin, Salmo
Twigg, Stephen R. F.
Weiner, Andrea Maria Julia
Armas, Pablo
Margarit, Ezequiel
Calcaterra, Nora Beatriz
Andersen, Gregers R.
McGowan, Simon J.
Wilkie, Andrew O. M.
Richieri Costa, Antonio
de Almeida, Maria L. G.
Passos Bueno, Maria Rita
author_role author
author2 Alvizi, Lucas
Zechi Ceide, Roseli M.
Bertola, Debora
Felix, Temis M.
de Souza, Josiane
Raskin, Salmo
Twigg, Stephen R. F.
Weiner, Andrea Maria Julia
Armas, Pablo
Margarit, Ezequiel
Calcaterra, Nora Beatriz
Andersen, Gregers R.
McGowan, Simon J.
Wilkie, Andrew O. M.
Richieri Costa, Antonio
de Almeida, Maria L. G.
Passos Bueno, Maria Rita
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 Noncoding Expansion
Richieri-Costa-Pereira Syndrome
Craniofacial Disorder
Limb Defects
topic Noncoding Expansion
Richieri-Costa-Pereira Syndrome
Craniofacial Disorder
Limb Defects
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 50 untranslated region (50 UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPSaffected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis.
Fil: Favaro, Francine P.. Universidade de Sao Paulo; Brasil
Fil: Alvizi, Lucas. Universidade de Sao Paulo; Brasil
Fil: Zechi Ceide, Roseli M.. Universidade de Sao Paulo; Brasil
Fil: Bertola, Debora. Universidade de Sao Paulo; Brasil
Fil: Felix, Temis M.. Universidade Federal do Rio Grande do Sul; Brasil
Fil: de Souza, Josiane. Centro de Atendimento Integral ao Fissurado La´bio Palatal; Brasil
Fil: Raskin, Salmo. Pontifícia Universidade Católica do Paraná. Núcleo de Investigação Molecular Avançada. Centro de Ciências Biológicas e da Saúde; Brasil
Fil: Twigg, Stephen R. F.. University of Oxford; Reino Unido
Fil: Weiner, Andrea Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Armas, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Margarit, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Calcaterra, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Andersen, Gregers R.. University Aarhus; Dinamarca
Fil: McGowan, Simon J.. University of Oxford; Reino Unido
Fil: Wilkie, Andrew O. M.. University of Oxford; Reino Unido
Fil: Richieri Costa, Antonio. Universidade de Sao Paulo; Brasil
Fil: de Almeida, Maria L. G.. Universidade de Sao Paulo; Brasil
Fil: Passos Bueno, Maria Rita. Universidade de Sao Paulo; Brasil
description Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 50 untranslated region (50 UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPSaffected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis.
publishDate 2014
dc.date.none.fl_str_mv 2014-01
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/11336/8819
Favaro, Francine P.; Alvizi, Lucas; Zechi Ceide, Roseli M.; Bertola, Debora; Felix, Temis M.; et al.; A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects; Cell Press; American Journal Of Human Genetics; 94; 1; 1-2014; 120-128
0002-9297
url http://hdl.handle.net/11336/8819
identifier_str_mv Favaro, Francine P.; Alvizi, Lucas; Zechi Ceide, Roseli M.; Bertola, Debora; Felix, Temis M.; et al.; A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects; Cell Press; American Journal Of Human Genetics; 94; 1; 1-2014; 120-128
0002-9297
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0002929713005351
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajhg.2013.11.020
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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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