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

TY - JOUR

T1 - An intellectual disability syndrome with single nucleotide variants in O-GlcNAc Transferase

AU - Pravata, Veronica

AU - Omelkova, Michaela

AU - Stavridis, Marios

AU - Desbiens, Chelsea M.

AU - Stephen, Hannah M.

AU - Lefeber, Dirk J.

AU - Gécz, Jozef

AU - Gundogdu, Mehmet

AU - Õunap, Katrin

AU - Joss, Shelagh

AU - Schwartz, Charles E.

AU - Wells, Lance

AU - van Aalten, Daan

N1 - Funding: Wellcome Trust WT087590MA

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.

KW - O-GlcNAc transferase

KW - O-GlcNAcylation

KW - X-linked intellectual disability

KW - neurodevelopment

UR - https://www.scopus.com/pages/publications/85080097527

U2 - 10.1038/s41431-020-0589-9

DO - 10.1038/s41431-020-0589-9

M3 - Article

C2 - 32080367

SN - 1018-4813

VL - 28

SP - 706

EP - 714

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 6

ER -