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

Area of Science:

• Biochemistry
• Genetics
• Developmental Biology

Background:

• The HYPK protein regulates the NatA complex, which is crucial for N-terminal protein acetylation.
• Dysregulation of protein acetylation is implicated in various neurodevelopmental disorders.

Purpose of the Study:

• To characterize the phenotype and molecular basis of a de novo HYPK variant.
• To investigate the impact of the variant on HYPK's inhibitory function and NatA-mediated acetylation.

Main Methods:

• Clinical evaluation of a proband with developmental delay, autism, and facial dysmorphia.
• Biochemical analyses to assess HYPK's interaction with the NatA complex.
• Assessment of N-terminal protein acetylation levels.

Main Results:

• A male proband presented with de novo HYPK variant, developmental delay, autism, and facial dysmorphia.
• The identified HYPK variant demonstrated enhanced inhibitory activity on the NatA complex.
• Pathogenic variant led to altered NatA-mediated N-terminal protein acetylation.

Conclusions:

• This is the first phenotypic characterization of a pathogenic HYPK variant.
• The molecular mechanism involves enhanced inhibition of the NatA complex, impacting protein acetylation.
• Findings will aid in the diagnosis and management of individuals with HYPK-related disorders.