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 orKAT6Agene are associated with a newlyidentified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity andspeech delay, hypotonia, and heart and eye malformations. Although loss of function...

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Autores: Urreizti, Roser, López-Martin, Estrella, Martínez-Monseny, Antonio, Pujadas, Montse, Castilla-Vallmanya, Laura, Pérez-Jurado, Luis Alberto, Serrano, Mercedes, Natera de Benito, Daniel, Martínez-Delgado, Beatriz, Posada-de-la-Paz, Manuel, Alonso, Javier, Marin-Reina, Purificación, O'Callaghan, Mar, Grinberg Vaisman, Daniel Raúl, Bermejo-Sánchez, Eva, Balcells Comas, Susana
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/168101
Acesso em linha:https://hdl.handle.net/2445/168101
Access Level:acceso abierto
Palavra-chave:Discapacitats mentals
Genètica
Mutació (Biologia)
People with mental disabilities
Genetics
Mutation (Biology)
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spelling Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrumUrreizti, RoserLópez-Martin, EstrellaMartínez-Monseny, AntonioPujadas, MontseCastilla-Vallmanya, LauraPérez-Jurado, Luis AlbertoSerrano, MercedesNatera de Benito, DanielMartínez-Delgado, BeatrizPosada-de-la-Paz, ManuelAlonso, JavierMarin-Reina, PurificaciónO'Callaghan, MarGrinberg Vaisman, Daniel RaúlBermejo-Sánchez, EvaBalcells Comas, SusanaDiscapacitats mentalsGenèticaMutació (Biologia)People with mental disabilitiesGeneticsMutation (Biology)Background:Pathogenic variants of the lysine acetyltransferase 6A orKAT6Agene are associated with a newlyidentified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity andspeech delay, hypotonia, and heart and eye malformations. Although loss of function (LoF) mutations were initiallyreported as causing this disorder, missense mutations, to date always involving serine residues, have recently beenassociated 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 missensechange and the only one not presenting with cardiac anomalies. The missense change [p.(Gly359Ser)], alsopredicted to affect splicing by in silico tools, was functionally tested in the patient's lymphocyte RNA revealing asplicing 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 withthe 80 cases previously reported, including developmental delay with speech delay, feeding difficulties, hypotonia, ahigh bulbous nose, and recurrent infections. Other features present in some of these five patients, such ascryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome.BioMed Central2020202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/168101Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s13023-020-1317-9Orphanet Journal of Rare Diseases, 2020, vol. 15, p. 44https://doi.org/10.1186/s13023-020-1317-9info:eu-repo/grantAgreement/EC/FP7/313010cc-by (c) Urreizti, Roser et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1681012026-05-29T05:05:01Z
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
Discapacitats mentals
Genètica
Mutació (Biologia)
People with mental disabilities
Genetics
Mutation (Biology)
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-Martin, Estrella
Martínez-Monseny, Antonio
Pujadas, Montse
Castilla-Vallmanya, Laura
Pérez-Jurado, Luis Alberto
Serrano, Mercedes
Natera de Benito, Daniel
Martínez-Delgado, Beatriz
Posada-de-la-Paz, Manuel
Alonso, Javier
Marin-Reina, Purificación
O'Callaghan, Mar
Grinberg Vaisman, Daniel Raúl
Bermejo-Sánchez, Eva
Balcells Comas, Susana
author Urreizti, Roser
author_facet Urreizti, Roser
López-Martin, Estrella
Martínez-Monseny, Antonio
Pujadas, Montse
Castilla-Vallmanya, Laura
Pérez-Jurado, Luis Alberto
Serrano, Mercedes
Natera de Benito, Daniel
Martínez-Delgado, Beatriz
Posada-de-la-Paz, Manuel
Alonso, Javier
Marin-Reina, Purificación
O'Callaghan, Mar
Grinberg Vaisman, Daniel Raúl
Bermejo-Sánchez, Eva
Balcells Comas, Susana
author_role author
author2 López-Martin, Estrella
Martínez-Monseny, Antonio
Pujadas, Montse
Castilla-Vallmanya, Laura
Pérez-Jurado, Luis Alberto
Serrano, Mercedes
Natera de Benito, Daniel
Martínez-Delgado, Beatriz
Posada-de-la-Paz, Manuel
Alonso, Javier
Marin-Reina, Purificación
O'Callaghan, Mar
Grinberg Vaisman, Daniel Raúl
Bermejo-Sánchez, Eva
Balcells Comas, Susana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Discapacitats mentals
Genètica
Mutació (Biologia)
People with mental disabilities
Genetics
Mutation (Biology)
topic Discapacitats mentals
Genètica
Mutació (Biologia)
People with mental disabilities
Genetics
Mutation (Biology)
description Background:Pathogenic variants of the lysine acetyltransferase 6A orKAT6Agene are associated with a newlyidentified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity andspeech delay, hypotonia, and heart and eye malformations. Although loss of function (LoF) mutations were initiallyreported as causing this disorder, missense mutations, to date always involving serine residues, have recently beenassociated 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 missensechange and the only one not presenting with cardiac anomalies. The missense change [p.(Gly359Ser)], alsopredicted to affect splicing by in silico tools, was functionally tested in the patient's lymphocyte RNA revealing asplicing 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 withthe 80 cases previously reported, including developmental delay with speech delay, feeding difficulties, hypotonia, ahigh bulbous nose, and recurrent infections. Other features present in some of these five patients, such ascryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome.
publishDate 2020
dc.date.none.fl_str_mv 2020
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 https://hdl.handle.net/2445/168101
url https://hdl.handle.net/2445/168101
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13023-020-1317-9
Orphanet Journal of Rare Diseases, 2020, vol. 15, p. 44
https://doi.org/10.1186/s13023-020-1317-9
info:eu-repo/grantAgreement/EC/FP7/313010
dc.rights.none.fl_str_mv cc-by (c) Urreizti, Roser et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Urreizti, Roser et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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