A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)

Detalhes bibliográficos
Autor(a) principal: Da Silva, Jorge Diogo
Data de Publicação: 2022
Outros Autores: Oliva-Teles, Natália, Tkachenko, Nataliya, Fino, Joana, Marques, Mariana, Fortuna, Ana Maria, David, Dezso
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/8588
Resumo: This article belongs to the Section Molecular Genetics and Genetic Diseases.
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spelling A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)CHD4-associated ND PhenotypeGSG1L2Sifrim–Hitz–Weiss Syndromedup(2)(q14.3q21.1)Familial TranslocationFrameshift CHD4 VariantDoenças GenéticasThis article belongs to the Section Molecular Genetics and Genetic Diseases.The genetic complexity of neurodevelopmental disorders (NDD), combined with a heterogeneous clinical presentation, makes accurate assessment of their molecular bases and pathogenic mechanisms challenging. Our purpose is to reveal the pathogenic variant underlying a complex NDD through identification of the "full" spectrum of structural genomic and genetic variants. Therefore, clinical phenotyping and identification of variants by genome and exome sequencing, together with comprehensive assessment of these and affected candidate genes, were carried out. A maternally-inherited familial translocation [t(17;19)(p13.1;p13.3)mat] disrupting the GSG1 like 2 gene (GSG1L2), a 3.2 Mb dup(2)(q14.3q21.1) encompassing the autosomal dominant OMIM phenotype-associated PROC and HS6ST1 gene, and a novel frameshift c.4442del, p.(Gly1481Valfs*21) variant within exon 30 of the Chromodomain helicase DNA binding protein 4 (CHD4) have been identified. Considering the pathogenic potential of each variant and the proband's phenotype, we conclude that this case basically fits the Sifrim-Hitz-Weiss syndrome or CHD4-associated neurodevelopmental phenotype. Finally, our data highlight the need for identification of the "full" spectrum of structural genomic and genetic variants and of reverse comparative phenotyping, including unrelated patients with variants in same genes, for improved genomic healthcare of patients with NDD.If this article is accepted for publication, Open Access publication will be funded by UMIB—Unidade Multidisciplinar de Investigação Biomédica, ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal/ITR—Laboratory for Integrative and Trans lational Research in Population Health, Porto, Portugal (https://umib.icbas.up.pt/, accessed on 14 December 2022), both supported by FCT—Fundação para a Ciência e a Tecnologia in the frameworks of UIDP/00215/2020; LA/P/0064/2020. This research was supported by national funds through FCT—Fundação para a Ciência e a Tecnologia, Research Grant HMSP-ICT/0016/2013 of the Harvard Medical School—Portugal Program in Translational Research and Information.MDPIRepositório Científico do Instituto Nacional de SaúdeDa Silva, Jorge DiogoOliva-Teles, NatáliaTkachenko, NataliyaFino, JoanaMarques, MarianaFortuna, Ana MariaDavid, Dezso2023-03-21T13:27:35Z2022-12-212022-12-21T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8588engBiomedicines. 2022 Dec 21;11(1):12. doi: 10.3390/biomedicines11010012.2227-905910.3390/biomedicines11010012info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:39Zoai:repositorio.insa.pt:10400.18/8588Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:43:13.973683Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
title A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
spellingShingle A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
Da Silva, Jorge Diogo
CHD4-associated ND Phenotype
GSG1L2
Sifrim–Hitz–Weiss Syndrome
dup(2)(q14.3q21.1)
Familial Translocation
Frameshift CHD4 Variant
Doenças Genéticas
title_short A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
title_full A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
title_fullStr A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
title_full_unstemmed A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
title_sort A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)
author Da Silva, Jorge Diogo
author_facet Da Silva, Jorge Diogo
Oliva-Teles, Natália
Tkachenko, Nataliya
Fino, Joana
Marques, Mariana
Fortuna, Ana Maria
David, Dezso
author_role author
author2 Oliva-Teles, Natália
Tkachenko, Nataliya
Fino, Joana
Marques, Mariana
Fortuna, Ana Maria
David, Dezso
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Da Silva, Jorge Diogo
Oliva-Teles, Natália
Tkachenko, Nataliya
Fino, Joana
Marques, Mariana
Fortuna, Ana Maria
David, Dezso
dc.subject.por.fl_str_mv CHD4-associated ND Phenotype
GSG1L2
Sifrim–Hitz–Weiss Syndrome
dup(2)(q14.3q21.1)
Familial Translocation
Frameshift CHD4 Variant
Doenças Genéticas
topic CHD4-associated ND Phenotype
GSG1L2
Sifrim–Hitz–Weiss Syndrome
dup(2)(q14.3q21.1)
Familial Translocation
Frameshift CHD4 Variant
Doenças Genéticas
description This article belongs to the Section Molecular Genetics and Genetic Diseases.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-21
2022-12-21T00:00:00Z
2023-03-21T13:27:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/8588
url http://hdl.handle.net/10400.18/8588
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biomedicines. 2022 Dec 21;11(1):12. doi: 10.3390/biomedicines11010012.
2227-9059
10.3390/biomedicines11010012
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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