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SHR Neuro Cancer Cardio Lipid Metab Microb

Nagy, D; Verheyen, S; Wigby, KM; Borovikov, A; Sharkov, A; Slegesky, V; Larson, A; Fagerberg, C; Brasch-Andersen, C; Kibæk, M; Bader, I; Hernan, R; High, FA; Chung, WK; Schieving, JH; Behunova, J; Smogavec, M; Laccone, F; Witsch-Baumgartner, M; Zobel, J; Duba, HC; Weis, D.
Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring.
Genes (Basel). 2022; 13(1): Doi: 10.3390/genes13010154 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Verheyen Sarah; Zobel Joachim
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Abstract:: POGZ-related disorders (also known as White-Sutton syndrome) encompass a wide range of neurocognitive abnormalities and other accompanying anomalies. Disease severity varies widely among POGZ patients and studies investigating genotype-phenotype association are scarce. Therefore, our aim was to collect data on previously unreported POGZ patients and perform a large-scale phenotype-genotype comparison from published data. Overall, 117 POGZ patients' genotype and phenotype data were included in the analysis, including 12 novel patients. A severity scoring system was developed for the comparison. Mild and severe phenotypes were compared with the types and location of the variants and the predicted presence or absence of nonsense-mediated RNA decay (NMD). Missense variants were more often associated with mild phenotypes (p = 0.0421) and truncating variants predicted to escape NMD presented with more severe phenotypes (p < 0.0001). Within this group, variants in the prolin-rich region of the POGZ protein were associated with the most severe phenotypes (p = 0.0004). Our study suggests that gain-of-function or dominant negative effect through escaping NMD and the location of the variants in the prolin-rich domain of the protein may play an important role in the severity of manifestations of POGZ-associated neurodevelopmental disorders.
Find related publications in this database (Keywords): POGZ gene; neurodevelopmental disorder; White-Sutton syndrome; genotype-phenotype association; clinical scoring; deep facial gestalt analysis; nonsense-mediated RNA decay