TY - JOUR
T1 - An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase
AU - Pravata, Veronica M.
AU - Omelková, Michaela
AU - Stavridis, Marios P.
AU - Desbiens, Chelsea M.
AU - Stephen, Hannah M.
AU - Lefeber, Dirk J.
AU - Gecz, Jozef
AU - Gundogdu, Mehmet
AU - Õunap, Katrin
AU - Joss, Shelagh
AU - Schwartz, Charles E.
AU - Wells, Lance
AU - van Aalten, Daan M.F.
N1 - Funding Information:
Funding This work was funded by a Wellcome Trust Senior Research Fellowship (WT087590MA) to DMFvA.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85080097527&partnerID=8YFLogxK
U2 - 10.1038/s41431-020-0589-9
DO - 10.1038/s41431-020-0589-9
M3 - Review article
C2 - 32080367
AN - SCOPUS:85080097527
VL - 28
SP - 706
EP - 714
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 6
ER -