Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Whole Exome Sequencing in Patients with Phenotypically Associated Familial Intracranial Aneurysm

  • Yunsun Song (Division of Neurointervention Clinic, Department of Radiology, Neurointervention Clinic, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jong-Keuk Lee (Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul) ;
  • Jin-Ok Lee (Department of Laboratory Medicine, Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Boseong Kwon (Division of Neurointervention Clinic, Department of Radiology, Neurointervention Clinic, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Eul-Ju Seo (Department of Laboratory Medicine, Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Dae Chul Suh (Division of Neurointervention Clinic, Department of Radiology, Neurointervention Clinic, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2021.06.11
  • Accepted : 2021.08.03
  • Published : 2022.01.01
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Abstract

Objective: Familial intracranial aneurysms (FIAs) are found in approximately 6%-20% of patients with intracranial aneurysms (IAs), suggesting that genetic predisposition likely plays a role in its pathogenesis. The aim of this study was to identify possible IA-associated variants using whole exome sequencing (WES) in selected Korean families with FIA. Materials and Methods: Among the 26 families in our institutional database with two or more IA-affected first-degree relatives, three families that were genetically enriched (multiple, early onset, or common site involvement within the families) for IA were selected for WES. Filtering strategies, including a family-based approach and knowledge-based prioritization, were applied to derive possible IA-associated variants from the families. A chromosomal microarray was performed to detect relatively large chromosomal abnormalities. Results: Thirteen individuals from the three families were sequenced, of whom seven had IAs. We noted three rare, potentially deleterious variants (PLOD3 c.1315G>A, NTM c.968C>T, and CHST14 c.58C>T), which are the most promising candidates among the 11 potential IA-associated variants considering gene-phenotype relationships, gene function, co-segregation, and variant pathogenicity. Microarray analysis did not reveal any significant copy number variants in the families. Conclusion: Using WES, we found that rare, potentially deleterious variants in PLOD3, NTM, and CHST14 genes are likely responsible for the subsets of FIAs in a cohort of Korean families.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2018R1A2B6003143).

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