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 funct...

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Autores: Urreizti R, Lopez-Martin E, Martinez-Monseny A, Pujadas M, Castilla-Vallmanya L, Pérez-Jurado LA, Serrano M, Natera-de Benito D, Martínez-Delgado B, Posada-de-la-Paz M, Alonso J, Marin-Reina P, O'Callaghan M, Grinberg D, Bermejo-Sánchez E, Balcells S
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p17396
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17396
Access Level:acceso abierto
Palabra clave:KAT6A
Neurodevelopmental disease
Clinical genetics
Whole exome sequencing
Clinical characterization
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spelling Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrumUrreizti RLopez-Martin EMartinez-Monseny APujadas MCastilla-Vallmanya LPérez-Jurado LASerrano MNatera-de Benito DMartínez-Delgado BPosada-de-la-Paz MAlonso JMarin-Reina PO'Callaghan MGrinberg DBermejo-Sánchez EBalcells SKAT6ANeurodevelopmental diseaseClinical geneticsWhole exome sequencingClinical characterizationBackground 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.BMC2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17396Orphanet Journal of Rare DiseasesISSN: 17501172reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p173962026-05-27T12:37:41Z
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 R
KAT6A
Neurodevelopmental disease
Clinical genetics
Whole exome sequencing
Clinical characterization
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 R
Lopez-Martin E
Martinez-Monseny A
Pujadas M
Castilla-Vallmanya L
Pérez-Jurado LA
Serrano M
Natera-de Benito D
Martínez-Delgado B
Posada-de-la-Paz M
Alonso J
Marin-Reina P
O'Callaghan M
Grinberg D
Bermejo-Sánchez E
Balcells S
author Urreizti R
author_facet Urreizti R
Lopez-Martin E
Martinez-Monseny A
Pujadas M
Castilla-Vallmanya L
Pérez-Jurado LA
Serrano M
Natera-de Benito D
Martínez-Delgado B
Posada-de-la-Paz M
Alonso J
Marin-Reina P
O'Callaghan M
Grinberg D
Bermejo-Sánchez E
Balcells S
author_role author
author2 Lopez-Martin E
Martinez-Monseny A
Pujadas M
Castilla-Vallmanya L
Pérez-Jurado LA
Serrano M
Natera-de Benito D
Martínez-Delgado B
Posada-de-la-Paz M
Alonso J
Marin-Reina P
O'Callaghan M
Grinberg D
Bermejo-Sánchez E
Balcells S
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv KAT6A
Neurodevelopmental disease
Clinical genetics
Whole exome sequencing
Clinical characterization
topic KAT6A
Neurodevelopmental disease
Clinical genetics
Whole exome sequencing
Clinical characterization
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
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://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17396
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17396
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv Orphanet Journal of Rare Diseases
ISSN: 17501172
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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