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

Roser Urreizti, Estrella Lopez-Martin, Antonio Martinez-Monseny, Montse Pujadas, Laura Castilla-Vallmanya, Luis Alberto Pérez-Jurado, Mercedes Serrano, Daniel Natera-De Benito, Beatriz Martínez-Delgado, Manuel Posada-De-La-Paz, Javier Alonso, Purificación Marin-Reina, Mar O'callaghan, Daniel Grinberg, Eva Bermejo-Sánchez, Susanna Balcells

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18 Citations (Scopus)


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.

Original languageEnglish
Article number44
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished or Issued - 10 Feb 2020
Externally publishedYes


  • Clinical characterization
  • Clinical genetics
  • KAT6A
  • Neurodevelopmental disease
  • Whole exome sequencing

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

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