Publication
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)
| dc.contributor.author | Da Silva, Jorge Diogo | |
| dc.contributor.author | Oliva-Teles, Natália | |
| dc.contributor.author | Tkachenko, Nataliya | |
| dc.contributor.author | Fino, Joana | |
| dc.contributor.author | Marques, Mariana | |
| dc.contributor.author | Fortuna, Ana Maria | |
| dc.contributor.author | David, Dezso | |
| dc.date.accessioned | 2023-03-21T13:27:35Z | |
| dc.date.available | 2023-03-21T13:27:35Z | |
| dc.date.issued | 2022-12-21 | |
| dc.description | This article belongs to the Section Molecular Genetics and Genetic Diseases. | pt_PT |
| dc.description.abstract | 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. | pt_PT |
| dc.description.sponsorship | 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. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Biomedicines. 2022 Dec 21;11(1):12. doi: 10.3390/biomedicines11010012. | pt_PT |
| dc.identifier.doi | 10.3390/biomedicines11010012 | pt_PT |
| dc.identifier.issn | 2227-9059 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/8588 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | MDPI | pt_PT |
| dc.relation | LA/P/0064/2020 | pt_PT |
| dc.relation | Unit for Multidisciplinary Research in Biomedicine | |
| dc.relation.publisherversion | https://www.mdpi.com/2227-9059/11/1/12 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.subject | CHD4-associated ND Phenotype | pt_PT |
| dc.subject | GSG1L2 | pt_PT |
| dc.subject | Sifrim–Hitz–Weiss Syndrome | pt_PT |
| dc.subject | dup(2)(q14.3q21.1) | pt_PT |
| dc.subject | Familial Translocation | pt_PT |
| dc.subject | Frameshift CHD4 Variant | pt_PT |
| dc.subject | Doenças Genéticas | pt_PT |
| dc.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) | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Unit for Multidisciplinary Research in Biomedicine | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00215%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0016%2F2013/PT | |
| oaire.citation.issue | 1 | pt_PT |
| oaire.citation.startPage | 12 | pt_PT |
| oaire.citation.title | Biomedicines | pt_PT |
| oaire.citation.volume | 11 | pt_PT |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.fundingStream | 3599-PPCDT | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.embargofct | Acesso de acordo com política editorial da revista. | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isProjectOfPublication | 3b59bbc6-7ac7-4600-b3e8-58aab73d3816 | |
| relation.isProjectOfPublication | 55f3392d-71be-4224-bedd-9feb4a06c428 | |
| relation.isProjectOfPublication.latestForDiscovery | 55f3392d-71be-4224-bedd-9feb4a06c428 |