Identification of novel CSNK2A1 variants and the genotype–phenotype relationship in patients with Okur–Chung neurodevelopmental syndrome: a case report and systematic literature review

• Published in: Journal of International Medical Research 2021-05, Vol.49 (5), p.3000605211017063-3000605211017063
• Main Authors: Wu, Ruo-hao, Tang, Wen-ting, Qiu, Kun-yin, Li, Xiao-juan, Tang, Dan-xia, Meng, Zhe, He, Zhan-wen
• Format: Article
• Language: English
• Subjects: Case reports; Genotype & phenotype; Mutation; Systematic Review
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/03000605211017063

De novo germline variants of the casein kinase 2α subunit (CK2α) gene (CSNK2A1) have been reported in individuals with the congenital neuropsychiatric disorder Okur–Chung neurodevelopmental syndrome (OCNS). Here, we report on two unrelated children with OCNS and review the literature to explore the genotype–phenotype relationship in OCNS. Both children showed facial dysmorphism, growth retardation, and neuropsychiatric disorders. Using whole-exome sequencing, we identified two novel de novo CSNK2A1 variants: c.479A>G p.(H160R) and c.238C>T p.(R80C). A search of the literature identified 12 studies that provided information on 35 CSNK2A1 variants in various protein-coding regions of CK2α. By quantitatively analyzing data related to these CSNK2A1 variants and their corresponding phenotypes, we showed for the first time that mutations in protein-coding CK2α regions appear to influence the phenotypic spectrum of OCNS. Mutations altering the ATP/GTP-binding loop were more likely to cause the widest range of phenotypes. Therefore, any assessment of clinical spectra for this disorder should be extremely thorough. This study not only expands the mutational spectrum of OCNS, but also provides a comprehensive overview to improve our understanding of the genotype–phenotype relationship in OCNS.