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Review
. 2024 Jan;12(1):e2327.
doi: 10.1002/mgg3.2327. Epub 2023 Nov 30.

Genetic analysis and literature review of a Poirier-Bienvenu neurodevelopmental syndrome family line caused by a de novo frameshift variant in CSNK2B

Danyang Li  1   2 , Bingbo Zhou  1 , Xinyuan Tian  1   2 , Xue Chen  1 , Yupei Wang  1 , Shengju Hao  1 , Chuan Zhang  1 , Ling Hui  1   2
Affiliations
Review

Genetic analysis and literature review of a Poirier-Bienvenu neurodevelopmental syndrome family line caused by a de novo frameshift variant in CSNK2B

Danyang Li et al. Mol Genet Genomic Med. 2024 Jan.

Abstract

Background: Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare autosomal dominant neurologic disorder caused by a heterozygous variant of CSNK2B, which is characterized by early onset epilepsy, hypotonia, varying degrees of intellectual disability (ID), developmental delay (DD), and facial dysmorphism. This study clarifies the molecular diagnosis and causative factors of a Chinese boy with POBINDS.

Methods: The clinical phenotypes and ancillary laboratory tests were collected and analyzed by trio whole exome sequencing (WES) and copy number variant sequencing (CNV-seq) in the follow-up proband's families. The candidate variant was validated by Sanger sequencing and bioinformatics software was used to further explore the effect of the de novo frameshift variant on the protein structure.

Results: The proband carries a de novo frameshift variant c.453_c.454insAC (p.H152fs*76) in CSNK2B. According to the ACMG genetic variant classification criteria and guidelines, the locus is a pathogenic variant (PVS1+PS2+PM2) and the associated disease was POBINDS. Protein structure prediction suggests significant differences in amino acid sequences before and after mutation.

Conclusion: A rare case of POBINDS caused by a novel frameshift variant in CSNK2B was diagnosed. The novel variant extends the variation spectrum of CSNK2B, which provides guidance for early clinical diagnosis, genetic counseling and treatment of this family. A review of the currently reported cases of POBINDS further enriches and summarizes the relationship between genotype and phenotype of POBINDS.

Keywords: CSNK2B; CNV-seq; Poirier-Bienvenu neurodevelopmental syndrome; WES; epilepsy; frameshift variant.

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Conflict of interest statement

The authors have nothing to declare.

Figures

FIGURE 1
FIGURE 1
Family tree of the proband.
FIGURE 2
FIGURE 2
Gecell Developmental Schedules (GDS) at 5 months of age. (a) Age of development (DA) perspective assessment. CA, chronological age. (b) Development quotient (DQ) perspective assessment. The patients had a mean DA of 3.5 months and a DQ score of 66, with scores of 60 for adaptation, 70 for gross motor, and 57 for fine motor, 75 for language, and 68 for personal socialization. The overall assessment was mild DD.
FIGURE 3
FIGURE 3
Sanger sequence of the affected family, with the sequencing validation sites shown by red arrows.
FIGURE 4
FIGURE 4
Predicted amino acid sequence before and after mutation, the black triangle shows the starting variant amino acid position. (a) Wild‐type amino acid sequence. (b) Mutant amino acid sequences.
FIGURE 5
FIGURE 5
Predicted protein secondary structure before and after mutation. (a) Wild‐type secondary structure prediction. (b) Mutant secondary structure prediction.
FIGURE 6
FIGURE 6
Predicted protein tertiary structure before and after mutation. (a) Wild‐type tertiary structure prediction. (b) Mutant tertiary structure prediction.
FIGURE 7
FIGURE 7
Characterization of the distribution of CSNK2B variants. (a) Map of variation type distribution. (b) The number of variant types.
See this image and copyright information in PMC

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