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Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation

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Abstract

Mutations in CSNK2B lead to Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), a rare neurodevelopmental disorder. Only 14 cases of POBINDS have been reported worldwide. The main manifestations are seizures, often tonic–clonic, with or without intellectual disability, growth retardation, and developmental language retardation. We conducted a comprehensive phenotypic mining and trio-whole exome sequencing on six children with POBINDS for gene diagnosis and analyzed the different variants using bioinformatics analysis software and related experiments. This paper reviews previous literature and discusses two common missense variants that lead to structural changes. Among the six patients, four, one, and one had tonic–clonic, myoclonic, and febrile seizures, respectively. Language development disorder, motor development disorder, and developmental delay/intellectual disability (DD/ID) are the main clinical features. All children had de novo mutations in CSNK2B, including three missense variants (c.410G > T/p.(Cys137Phe), c.494A > G/p.(His165Arg), and c.3G > A/p.(Met1Ile)), two splice variants (c.292-2A > T, c.558-3 T > G), and one frameshift variant (c.499delC/p.(Leu167Serfs*60)). Three missense variants were predicted to be harmful by various software programs, and two splicing variants were found to produce new exonic splicing enhancers by the minigene assay. Western blot analysis showed that the frameshift variant resulted in decreased protein expression. According to a literature review, c.3G > A/p.(Met1Ile), c.292-2A > T, c.558-3 T > G, and c.499delC/p.(Leu167Serfs*60) are novel variants of CSNK2B. The decrease or loss of protein function caused by CSNK2B mutations may be a pathogenic factor in this cohort. The severity of the POBINDS phenotype differs, and refractory epilepsy may be accompanied by a more serious DD/ID, language disorder, and motor retardation. At present, there is no specific treatment, and antiepileptic therapy usually requires the combination of two or more anti-epileptic drugs.

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The data are available on request from the corresponding author.

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Acknowledgements

We are sincerely grateful to the family members for their participation in this study. We thank the staff of Chigene (Beijing) Translational Medical Research Center Co. Ltd. for providing next-generation sequencing, analyzing genetic diseases, and discussion.

Funding

The study was supported by the Scientific Research Project of Hunan Provincial Health Commission (subject ID: B2019015).

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Authors and Affiliations

  1. Department of Neurology, Hunan Children’s Hospital, Ziyuan Road & No. 86, Changsha, 410001, Hunan, China

    Sai Yang, Liwen Wu, Hongmei Liao, Xiulan Lu, Xiao Zhang, Xiaojun Kuang & Liming Yang

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  1. Sai Yang
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  2. Liwen Wu
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  3. Hongmei Liao
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  4. Xiulan Lu
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  5. Xiao Zhang
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  6. Xiaojun Kuang
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  7. Liming Yang
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Contributions

LY investigated the subject and conceived the targets. SY designed the study and drafted the manuscript. SY and LW were responsible for the genetic analysis. SY, LW, HL, XL, XZ, and XK performed clinical tests on patients. LW, HL, and XL collected information on the reported. LY critically reviewed the manuscript. All authors approved the final copy of the manuscript submitted for publication.

Corresponding author

Correspondence to Liming Yang.

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Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki and approved by the Medical Ethics Committee of Hunan Children’s Hospital (Hunan Province, China).

Conflict of interest

The authors declare no competing interests.

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Yang, S., Wu, L., Liao, H. et al. Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation. Neurogenetics 22, 323–332 (2021). https://doi.org/10.1007/s10048-021-00649-2

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  • DOI: https://doi.org/10.1007/s10048-021-00649-2

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