Urreizti, RoserLópez Martín, EstrellaMartínez Monseny, Antonio FedericoPujadas, MontseCastilla-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, Susana2020-04-222020-04-222020Urreizti 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. Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum. Orphanet J Rare Dis. 2020; 15(1):44. DOI: 10.1186/s13023-020-1317-91750-1172http://hdl.handle.net/10230/44304Background: 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13023-020-1317-9Clinical characterizationClinical geneticsKAT6ANeurodevelopmental diseaseWhole exome sequencinginfo:eu-repo/semantics/openAccess