Whole Exome Sequencing in Patients with Phenotypically Associated Familial Intracranial Aneurysm
- Author:
Yunsun SONG
1
;
Jong-Keuk LEE
;
Jin-Ok LEE
;
Boseong KWON
;
Eul-Ju SEO
;
Dae Chul SUH
Author Information
- Publication Type:Original Article
- From:Korean Journal of Radiology 2022;23(1):101-111
- CountryRepublic of Korea
- Language:English
-
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.
