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Published on: April 4, 2018
A Phenotype-Based Score to Prioritize RNF213 p.R4810K Genotyping in Isolated Intracranial Steno-Occlusive Disease
Dong Young Jeong1,2, Chulhong Kim1,3,4,5,6, Dougho Park7,8
1School of Convergence Science and Technology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Translational Stroke Research
|August 1, 2026
Summary
A new score helps identify patients with intracranial arterial steno-occlusive disease (ICAD) who are likely to carry the RNF213 p.R4810K variant. This approach prioritizes genetic testing, improving efficiency in resource-limited settings.
Area of Science:
- Genetics
- Neurology
- Vascular Medicine
Background:
- Ring finger protein 213 (RNF213) p.R4810K is a key genetic factor for intracranial arteriopathies.
- Intracranial arterial steno-occlusive disease (ICAD) presents diagnostic challenges, particularly in differentiating it from Moyamoya disease (MMD).
- Efficient identification of RNF213 p.R4810K carriers is crucial for understanding and managing ICAD.
Purpose of the Study:
- To develop and validate a phenotype-based triage score for prioritizing RNF213 genotyping in patients with isolated ICAD.
- To enhance the probability of identifying RNF213 p.R4810K carriage through clinical phenotyping.
- To improve the efficiency of genetic testing for RNF213 in clinical practice.
Main Methods:
- Retrospective analysis of 753 patients with isolated ICAD undergoing RNF213 genotyping.
- Development of a score incorporating anterior cerebral artery (ACA) laterality, tandem lesion burden, and Moyamoya disease (MMD) family history.
- Assessment of score discrimination and calibration, with external validation in an independent cohort.
Main Results:
- RNF213 p.R4810K was found in 38.4% of patients.
- MMD family history, tandem lesion burden, and ACA laterality were significantly associated with RNF213 p.R4810K carriage.
- A score cutoff of ≥3 reduced genotyping by 66.5% while capturing 55.7% of carriers, with moderate discrimination (AUC 0.708-0.720).
Conclusions:
- A phenotype-based score integrating lesion distribution and family history can effectively prioritize RNF213 genotyping in isolated ICAD.
- This approach offers a practical solution for improving genotyping yield in resource-limited settings.
- The score aids in efficient patient selection for genetic testing, optimizing diagnostic workflows.
