Variants in NAA15 were first reported in individuals with intellectual disability and autism by Stessman et al. in 2017 (PMID: 28191889), in a case cohort study of neurodevelopmental disorders in which 13 individuals with NAA15 variants were described. Two additional case series have subsequently been published (PMIDs: 29656860, 31127942), with over 40 probands in total described in the literature. Affected individuals typically harbor de novo heterozygous truncating variants, although milder cases with missense variants and inheritance in families have been documented. Phenotypic features include variable levels of intellectual disability, motor and speech delay, and autism spectrum disorder. Some individuals also present with dysmorphic features, cardiac abnormalities, and seizures.
NAA15 encodes the enzyme N-alpha-Acetyltransferase 15, a subunit of the NatA complex involved in co-translational acetylation of the peptide N-terminus. This gene-disease relationship is also supported by experimental evidence, including protein interaction with NAA10, involved in a neurodevelopmental disorder, and functional alterations in non-patient cells (PMIDs: 29656860, 33557580).
In summary, there is definitive evidence supporting the relationship between NAA15 and autosomal dominant syndromic intellectual disability. This classification was approved by the Intellectual Disability and Autism Gene Curation Expert Panel on January 5, 2022 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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