Journal Article

Whole Exome Sequencing in Patients with Phenotypically Associated Familial Intracranial Aneurysm

Lee, Jin-Ok, Lee, Jong-Keuk, Kwon, Boseong, Seo, Eul-Ju, Song, Yunsun, Suh, Dae Chul

2022

Overview

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. 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. Thirteen individuals from the three families were sequenced, of whom seven had IAs. We noted three rare, potentially deleterious variants ( c.1315G>A, c.968C>T, and 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. Using WES, we found that rare, potentially deleterious variants in , , and genes are likely responsible for the subsets of FIAs in a cohort of Korean families.

• Publisher: The Korean Society of Radiology,대한영상의학회
• Subject: Aneurysms / Carotid arteries / Consortia / Genes / Genetic Predisposition to Disease / Genomes / Genomics / Genotype & phenotype / Humans / Intracranial Aneurysm - genetics / Medical imaging / Neurointervention / Pedigree / Phenotype / Siblings / Veins & arteries / Whole Exome Sequencing / 방사선과학