Projects per year
X-linked Intellectual Disabilities (XLID) are common developmental disorders. The enzyme O-GlcNAc transferase encoded by OGT, a recently discovered XLID gene, attaches O-GlcNAc to nuclear and cytoplasmic proteins. As few missense mutations have been described, it is unclear what the aetiology of the patient phenotypes is. Here, we report the discovery of a missense mutation in the catalytic domain of OGT in an XLID patient. X-ray crystallography reveals that this variant leads to structural rearrangements in the catalytic domain. The mutation reduces in vitro OGT activity on substrate peptides/protein. Mouse embryonic stem cells carrying the mutation reveal reduced O-GlcNAcase (OGA) and global O-GlcNAc levels. These data suggest a direct link between changes in the O-GlcNAcome and intellectual disability observed in patients carrying OGT mutations.
- OGlcNAC transferase
- intellectual disability
Deciphering the causes and effects of O-GlcNAc Transferase nucleotide variants in neurodevelopmental disordersAuthor: Pravata, V. M., 2021
Supervisor: van Aalten, D. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy