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Loop-region mutations in CSNK2A1 are associated with higher symptom burden in OCNDS

In 48 individuals with OCNDS, variants in loop regions of CK2α were associated with significantly younger age at diagnosis and higher frequency of hypotonia. Mutations in the glycine-rich loop were linked to significantly higher symptom burden and more non-seizure neurological symptoms.

Last updated: Aug 26, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score32/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. OCNDS core features are conserved across variants, with loop-region mutations driving greater symptom burden.

observational

Bagatelas ED, Khan MM, Rushing GV · Frontiers in human neuroscience (2026)

Participants: N/A
Duration: N/A
Intervention: Genetic variant location (loop vs. non-loop regions of CK2α protein)
Outcome: Age at diagnosis, symptom burden, frequency of hypotonia, non-seizure neurological symptoms
Effect Size: N/A
Population: 48 individuals with pathogenic or likely pathogenic CSNK2A1 missense variants enrolled in Simons Searchlight

Result:

PubMed: 40677894DOI: 10.3389/fnhum.2025.1589897

Mechanism Graph

Mutations in loop regions (e.g., glycine-rich loop) disrupt ATP binding and regulatory CK2β subunit interaction
↓
Disrupted CK2α function alters downstream signaling pathways
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Increased functional impairment leads to greater symptom burden
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Result: Higher symptom burden and earlier diagnosis in loop-region variants

Limitations

  • ⚠Small sample size (n=48) limits generalizability
  • ⚠Reliance on caregiver-reported surveys may introduce bias
  • ⚠No functional assays performed to confirm mechanistic links

Frequently Asked Questions

What is OCNDS?▼

Okur-Chung Neurodevelopmental Syndrome is an ultra-rare genetic disorder caused by mutations in the CSNK2A1 gene, characterized by developmental delay, intellectual disability, and speech deficits.

Which mutations cause more severe symptoms?▼

Mutations in loop regions, particularly the glycine-rich loop, are associated with higher symptom burden and earlier diagnosis.

Are sleep issues affected by mutation location?▼

No significant differences were observed between variant locations for sleep issues, intellectual disability, or speech delay.

How many patients were studied?▼

The study analyzed natural history data from 48 individuals with pathogenic CSNK2A1 missense variants.

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References

  1. 1.Bagatelas ED, Khan MM, Rushing GV. "OCNDS core features are conserved across variants, with loop-region mutations driving greater symptom burden.." Frontiers in human neuroscience, 2026. PMID: 40677894 DOI: 10.3389/fnhum.2025.1589897
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.