Urreizti, 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, Susana2020-07-082020-07-082020-02-101750-1172https://hdl.handle.net/2445/168101Background: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.14 p.application/pdfengcc-by (c) Urreizti, Roser et al., 2020http://creativecommons.org/licenses/by/3.0/esDiscapacitats mentalsGenèticaMutació (Biologia)People with mental disabilitiesGeneticsMutation (Biology)info:eu-repo/semantics/article6951092020-07-08info:eu-repo/semantics/openAccess32041641