MG-116 Determining a genetic cause for familial intracranial aneurysms. (4th December 2015)

• Record Type: Journal Article
• Authors: Hitchcock, Emma; Diamond, Jillian; Townsend, Katelin; Chung, Brian; Gibson, William
• Is Part Of: Journal of medical genetics. Volume 52(2015)Supplement 2
• Page Start: A6
• Page End: A6
• Publication Date: 2015-12-04
• Subjects: Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2015-103578.16
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Intracranial berry aneurysms (IA) can develop in arterial walls where the endothelial layer has weakened. Subarachnoid haemorrhage (SAH) occurs when an IA bursts causing blood to flow into the brain space. SAH leads to death in 35–50% of patients, and to brain damage in 25–50% of survivors. Familial IA (FIA) is suspected when a patient has two or more first-degree relatives with IA or SAH. The risk for a ruptured aneurysm in an individual with FIA is 17 times greater compared to the general population. Currently, there is no genetic test to assess the risk of developing an IA, and repeated brain imaging tests are required to screen those at risk as affected individuals are often asymptomatic. We have identified a family with a history of FIA spanning over three-generations, with three affected and four unaffected siblings. The inheritance pattern of FIA in this family appears to be autosomal dominant, strongly suggestive of a true Mendelian disorder. Our hypothesis is that there will be a single rare pathogenic variant that leads to the development of FIA in this family. We have collected DNA samples from this family, and carried out whole-genome SNP microarray on DNA from one affected and four unaffected siblings. We also performed whole-exome sequencing (WES) on one of the affected siblings. We will further filter our list of candidate genes created from genomic areas of interest that were identified from the microarray data using our list of rare, predicted damaging, variants generated from the WES data. These areas of interest will include regions shared between affected individuals, and exclude those shared with unaffected individuals. This family is unique to our knowledge, and our research could lead to the first identification of a monogenic cause for IA.