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2023 ACMG Annual Clinical Genetics Meeting Digital ...
Identification of novel variants and phenotypic ex ...
Identification of novel variants and phenotypic expansion in OGT-CDG
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This document discusses the identification of novel variants and phenotypic expansion in OGT-CDG (OGT-associated Congenital Disorder of Glycosylation), a rare genetic disorder characterized by intellectual disability and developmental delays. The study describes three patients with maternally inherited missense variants in the OGT gene. <br /><br />The clinical presentation of the patients showed phenotypical variability, including motor delay, intellectual disability, limb abnormalities, and behavioral involvement. The study performed assays on patient-derived fibroblasts and age-matched controls to assess OGT and OGA (O-GlcNAcase) protein expression and HCF1 processing. The results indicated no significant alterations in OGT and OGA protein expression but a decrease in cleaved HCF1 over full-length HCF1, suggesting reduced proteolytic processing by the OGT TPR domain. <br /><br />The researchers emphasized the importance of identifying additional OGT-CDG patients to enhance understanding of the disease's clinical presentation and the role of the O-GlcNAc system. They also highlighted the need for further research to investigate the impact of identified variants on OGT protein stability and O-GlcNAcylation to gain more insights into the mechanisms underlying OGT-CDG.<br /><br />In conclusion, this study adds to the existing knowledge of OGT-CDG by identifying novel variants and expanding the phenotypic spectrum. The findings contribute to a better understanding of X-linked CDG mechanisms and underscore the importance of functional characterization of OGT variants to explore their impact on disease development.
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Presenting Author - jan verheijen, PhD; Co-Author - Lotte Vanhye, Msc; Co-Author - Ayesha Niaz Shaikh, MD; Co-Author - Silvia Radenkovic, PhD; Co-Author - Wasantha Ranatunga, PhD; Co-Author - Pavel Pichurin, MD; Co-Author - Joan Steyermark, CGC; Co-Author - Eric Klee; Co-Author - Eva Morava-Kozicz, MD, PhD;
Meta Tag
Brain/Nervous System
Genotype-Phenotype Correlations
Intellectual disability
Metabolic Disorder
X-Inactivation/X-Linked Disease
Co-Author
Lotte Vanhye, Msc
Co-Author
Ayesha Niaz Shaikh, MD
Co-Author
Silvia Radenkovic, PhD
Co-Author
Wasantha Ranatunga, PhD
Co-Author
Pavel Pichurin, MD
Co-Author
Joan Steyermark, CGC
Co-Author
Eric Klee
Co-Author
Eva Morava-Kozicz, MD, PhD
Presenting Author
jan verheijen, PhD
Keywords
novel variants
phenotypic expansion
OGT-CDG
genetic disorder
intellectual disability
developmental delays
missense variants
OGT gene
motor delay
limb abnormalities
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