Details

Autor(en) / Beteiligte

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

Titel

Whole Exome Sequencing in Patients with Phenotypically Associated Familial Intracranial Aneurysm

Ist Teil von

• Korean Journal of Radiology, 2022, 23(1), , pp.101-111

Ort / Verlag

Korea (South): The Korean Society of Radiology

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.