HYPK-Related Neurodevelopmental Syndrome: Case Report of Intellectual Disability, Developmental Delay, and Dysmorphic Features.

HYPK is a critical modulator and inhibitor of the NatA complex. Here, we report a male proband with a de novo HYPK variant presenting with developmental delay, autism, and facial dysmorphia. Biochemical analyses show that this pathogenic variant enhances the inhibitory activity of HYPK on NatA-mediated N-terminal protein acetylation. Our findings provide the first phenotypic characterization of a pathogenic HYPK variant and elucidate its molecular basis, which will facilitate future diagnosis and management in similar cases worldwide.