<scp>HYPK</scp> ‐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.
Authors
- Shu‐ou Shan (ORCID: https://orcid.org/0000-0002-6526-1733)
- Gholson J. Lyon (ORCID: https://orcid.org/0000-0002-5869-0716)
- Rikhil Makwana
- Ingrid M. Wentzensen (ORCID: https://orcid.org/0000-0001-6994-1640)
- Elaine Marchi
- Tzung‐Chien Hsieh (ORCID: https://orcid.org/0000-0003-3828-4419)
- Philip F. Giampietro (ORCID: https://orcid.org/0000-0001-5151-6152)
- Ziyi Fan (ORCID: https://orcid.org/0000-0003-3793-2445)
- Rahi Patel (ORCID: https://orcid.org/0000-0001-8687-1197)
- Beatriz Menéndez
- Erin Falsey
Institutions
- California Institute of Technology (US)
- University of Bonn (DE)
- City University of New York (US)
- University Hospital Bonn (DE)
- New York State Office for People With Developmental Disabilities (US)
- University of Illinois Chicago (US)
- Shriners Hospitals for Children - Chicago (US)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2025-08-05
- DOI
- https://doi.org/10.1111/cge.70039
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Office for People With Developmental Disabilities
- National Institutes of Health
- National Institute of General Medical Sciences