A Case of CSNK2A1 Gene Variant Causing Okur-Chung Syndrome and Analysis of the Clinical Phenotypic Spectrum.

backgroudTo investigate the clinical features and genetic etiology of one child with Okur-Chung neurodevelopmental syndrome (OCNDS). The pathogenic variation spectrum of the CSNK2A1 gene and the phenotype spectrum of OCNDS were analyzed retrospectively.

methodsA patient was selected from the endocrinology department of Dongying People's Hospital in July 2024. The genetic etiology of the phenotypic abnormality was identified by whole-exome sequencing (WES). All previously reported cases of OCNDS were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, and the ClinVar database, and the phenotype and pathogenicity of the CSNK2A1 gene were retrospectively summarized. The differences in the mutation location and clinical phenotype of the CSNK2A1 gene were analyzed in combination with the literature on cell and molecular genetics.

resultsOne variant (NM_001895.4: c.149A>G:p.Tyr50Cys) were de novo and previously reported within the CSNK2A1 gene and has been identified as a potential cause of OCNDS. The clinical data of 65 patients with OCNDS were retrospectively analyzed. The main clinical characteristics of OCNDS were developmental retardation of the nervous system, intellectual disability, facial deformity, language disorder, and other system abnormalities. This specific variant is located within the Glycine-Rich loop domain. There were significant differences in sleep disorders, autism spectrum disorders, short stature, and developmental delays.

conclusionThis study diagnosed an OCNDS patient caused by a heterozygous mutation NM_001895.4: c.149A>G:p.Tyr50Cys in the CSNK2A1 gene through exome sequencing technology, further expanding the pathogenic variant spectrum of this gene. A systematic literature review and analysis was conducted to provide a foundation for the subsequent demonstration, which was based on the findings of the review. The demonstration revealed that variants in critical residues within the kinase domain disrupt the protein's spatial conformation and impair its function. This provides molecular evidence for genotype-phenotype correlation. These findings contribute to the advancement of knowledge in the field of OCNDS pathogenesis and provide a foundation for the development of genetic counselling and targeted therapeutic interventions.