Dataset Information

Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring.

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.

SUBMITTER: Nagy D

PROVIDER: S-EPMC8775410 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring.

Nagy Dóra D Verheyen Sarah S Wigby Kristen M KM Borovikov Artem A Sharkov Artem A Slegesky Valerie V Larson Austin A Fagerberg Christina C Brasch-Andersen Charlotte C Kibæk Maria M Bader Ingrid I Hernan Rebecca R High Frances A FA Chung Wendy K WK Schieving Jolanda H JH Behunova Jana J Smogavec Mateja M Laccone Franco F Witsch-Baumgartner Martina M Zobel Joachim J Duba Hans-Christoph HC Weis Denisa D

Genes 20220115 1

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 phenot ...[more]

PMID: 35052493

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Dataset Information

Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring.

Publications

Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring.

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