An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase

Veronica M. Pravata, Michaela Omelková, Marios P. Stavridis, Chelsea M. Desbiens, Hannah M. Stephen, Dirk J. Lefeber, Jozef Gecz, Mehmet Gundogdu, Katrin Õunap, Shelagh Joss, Charles E. Schwartz, Lance Wells, Daan M.F. van Aalten

Research output: Contribution to journalReview article

Abstract

Intellectual disability (ID) is a neurodevelopmental condition that affects ~1% of the world population. In total 5−10% of ID cases are due to variants in genes located on the X chromosome. Recently, variants in OGT have been shown to co-segregate with X-linked intellectual disability (XLID) in multiple families. OGT encodes O-GlcNAc transferase (OGT), an essential enzyme that catalyses O-linked glycosylation with β-N-acetylglucosamine (O-GlcNAc) on serine/threonine residues of thousands of nuclear and cytosolic proteins. In this review, we compile the work from the last few years that clearly delineates a new syndromic form of ID, which we propose to classify as a novel Congenital Disorder of Glycosylation (OGT-CDG). We discuss potential hypotheses for the underpinning molecular mechanism(s) that provide impetus for future research studies geared towards informed interventions.

Original languageEnglish
Pages (from-to)706-714
Number of pages9
JournalEuropean Journal of Human Genetics
Volume28
Issue number6
DOIs
Publication statusPublished - 1 Jun 2020

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Pravata, V. M., Omelková, M., Stavridis, M. P., Desbiens, C. M., Stephen, H. M., Lefeber, D. J., ... van Aalten, D. M. F. (2020). An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase. European Journal of Human Genetics, 28(6), 706-714. https://doi.org/10.1038/s41431-020-0589-9