Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum

Background: Pathogenic variants of the lysine acetyltransferase 6A or KAT6A gene are associated with a newly identified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity and speech delay, hypotonia, and heart and eye malformations. Although loss of func...

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Autores: Urreizti, Roser, López Martín, Estrella, Martínez Monseny, Antonio Federico, Pujadas, Montserrat, Castilla-Vallmanya, Laura, Pérez Jurado, Luis Alberto, Serrano, Mercedes L., Natera de Benito, Daniel, Martínez Delgado, Beatriz, Posada de la Paz, Manuel, Alonso, Javier, Marín Reina, Purificación, O'Callaghan, Mar, Grinberg, Daniel, Bermejo Sánchez, Eva, Balcells, Susana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44304
Acceso en línea:http://hdl.handle.net/10230/44304
http://dx.doi.org/10.1186/s13023-020-1317-9
Access Level:acceso abierto
Palabra clave:Clinical characterization
Clinical genetics
KAT6A
Neurodevelopmental disease
Whole exome sequencing
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spelling Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrumUrreizti, RoserLópez Martín, EstrellaMartínez Monseny, Antonio FedericoPujadas, Montserrat Castilla-Vallmanya, LauraPérez Jurado, Luis AlbertoSerrano, Mercedes L.Natera de Benito, DanielMartínez Delgado, BeatrizPosada de la Paz, ManuelAlonso, JavierMarín Reina, PurificaciónO'Callaghan, MarGrinberg, DanielBermejo Sánchez, EvaBalcells, SusanaClinical characterizationClinical geneticsKAT6ANeurodevelopmental diseaseWhole exome sequencingBackground: Pathogenic variants of the lysine acetyltransferase 6A or KAT6A gene are associated with a newly identified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity and speech delay, hypotonia, and heart and eye malformations. Although loss of function (LoF) mutations were initially reported as causing this disorder, missense mutations, to date always involving serine residues, have recently been associated with a form of the disorder without cardiac involvement. Results: In this study we present five new patients, four with truncating mutations and one with a missense change and the only one not presenting with cardiac anomalies. The missense change [p.(Gly359Ser)], also predicted to affect splicing by in silico tools, was functionally tested in the patient’s lymphocyte RNA revealing a splicing effect for this allele that would lead to a frameshift and premature truncation. Conclusions: An extensive revision of the clinical features of these five patients revealed high concordance with the 80 cases previously reported, including developmental delay with speech delay, feeding difficulties, hypotonia, a high bulbous nose, and recurrent infections. Other features present in some of these five patients, such as cryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome.Funding was from Associació Síndrome Opitz C, Terrassa, Spain; Spanish Ministerio de Economía y Competitividad (SAF2016–75948-R) and from CIBERER (U720). SpainUDP is an initiative funded by the Instituto de Salud Carlos III. Also, the whole exome sequencing of patient 3 was funded through 2016 BBMRI-LPC Call (FP7/2007–2013, grant agreement n° 313010) and patient 5 was sequenced thanks to the PERIS·URDCat program, funded by the Departament de Salut de la Generalitat de Catalunya (PERIS_SLT002_16_00174).BioMed Central202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44304http://dx.doi.org/10.1186/s13023-020-1317-9reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésOrphanet J Rare Dis. 2020; 15(1):44info:eu-repo/grantAgreement/EC/FP7/313010info:eu-repo/grantAgreement/ES/1PE/SAF2016–75948-R© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/443042026-06-12T07:21:37Z
dc.title.none.fl_str_mv Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
title Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
spellingShingle Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
Urreizti, Roser
Clinical characterization
Clinical genetics
KAT6A
Neurodevelopmental disease
Whole exome sequencing
title_short Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
title_full Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
title_fullStr Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
title_full_unstemmed Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
title_sort Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum
dc.creator.none.fl_str_mv Urreizti, Roser
López Martín, Estrella
Martínez Monseny, Antonio Federico
Pujadas, Montserrat
Castilla-Vallmanya, Laura
Pérez Jurado, Luis Alberto
Serrano, Mercedes L.
Natera de Benito, Daniel
Martínez Delgado, Beatriz
Posada de la Paz, Manuel
Alonso, Javier
Marín Reina, Purificación
O'Callaghan, Mar
Grinberg, Daniel
Bermejo Sánchez, Eva
Balcells, Susana
author Urreizti, Roser
author_facet Urreizti, Roser
López Martín, Estrella
Martínez Monseny, Antonio Federico
Pujadas, Montserrat
Castilla-Vallmanya, Laura
Pérez Jurado, Luis Alberto
Serrano, Mercedes L.
Natera de Benito, Daniel
Martínez Delgado, Beatriz
Posada de la Paz, Manuel
Alonso, Javier
Marín Reina, Purificación
O'Callaghan, Mar
Grinberg, Daniel
Bermejo Sánchez, Eva
Balcells, Susana
author_role author
author2 López Martín, Estrella
Martínez Monseny, Antonio Federico
Pujadas, Montserrat
Castilla-Vallmanya, Laura
Pérez Jurado, Luis Alberto
Serrano, Mercedes L.
Natera de Benito, Daniel
Martínez Delgado, Beatriz
Posada de la Paz, Manuel
Alonso, Javier
Marín Reina, Purificación
O'Callaghan, Mar
Grinberg, Daniel
Bermejo Sánchez, Eva
Balcells, Susana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Clinical characterization
Clinical genetics
KAT6A
Neurodevelopmental disease
Whole exome sequencing
topic Clinical characterization
Clinical genetics
KAT6A
Neurodevelopmental disease
Whole exome sequencing
description Background: Pathogenic variants of the lysine acetyltransferase 6A or KAT6A gene are associated with a newly identified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity and speech delay, hypotonia, and heart and eye malformations. Although loss of function (LoF) mutations were initially reported as causing this disorder, missense mutations, to date always involving serine residues, have recently been associated with a form of the disorder without cardiac involvement. Results: In this study we present five new patients, four with truncating mutations and one with a missense change and the only one not presenting with cardiac anomalies. The missense change [p.(Gly359Ser)], also predicted to affect splicing by in silico tools, was functionally tested in the patient’s lymphocyte RNA revealing a splicing effect for this allele that would lead to a frameshift and premature truncation. Conclusions: An extensive revision of the clinical features of these five patients revealed high concordance with the 80 cases previously reported, including developmental delay with speech delay, feeding difficulties, hypotonia, a high bulbous nose, and recurrent infections. Other features present in some of these five patients, such as cryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44304
http://dx.doi.org/10.1186/s13023-020-1317-9
url http://hdl.handle.net/10230/44304
http://dx.doi.org/10.1186/s13023-020-1317-9
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Orphanet J Rare Dis. 2020; 15(1):44
info:eu-repo/grantAgreement/EC/FP7/313010
info:eu-repo/grantAgreement/ES/1PE/SAF2016–75948-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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