Relevance to Autism

A de novo frameshift variant in the KAT6A gene has been identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Variants in this gene are associated with autosomal dominant mental retardation-32 (MRD32; OMIM 616268). One of the four patients with a de novo KAT6A nonsense variant and intellectual disability that was identified in Arboleda et al., 2015 was also diagnosed with ASD. An additional patient with ASD, intellectual disability, and epilepsy was found to have a de novo splice-site variant in KAT6A in Millan et al., 2016; however, this patient also had a sister with ID and autism, and the presence of the KAT6A variant in her was not reported. A review of the clinical phenotypes of 52 previously unreported individuals with pathogenic KAT6A variants in Kennedy et al., 2018 found that autism and autistic features were reported in approximately 25% of cases. St. John et al., 2022 described the phenotypic presentation of 49 individuals with pathogenic KAT6A variants and found that developmental delay/intellectual disability (42/45) was the most common phenotype observed in this cohort, along with concerns about vision (37/48), gastrointestinal function (33/48), and sleep (31/48); one-third (10/31) had a diagnosis of autism, and 73% (36/49) were minimally verbal.

Molecular Function

This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases and is part of a complex that acetylates lysine-9 residues in histone 3. In addition, it acts as a co-activator for several transcription factors. Variants in this gene are associated with autosomal dominant mental retardation-32 (MRD32; OMIM 616268).

External Links

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