Annually, over 30,000 people in the U.S. suffer from subarachnoid hemorrhage due to a ruptured cerebral aneurysm, with nearly 60% fatality. Little is known about susceptibility to intracranial aneurysm (IA), although it is well recognized that there is a familial component, likely to be genetic in origin. No studies have directly addressed or identified a genetic link. Identification of a susceptibility locus could potentially alter the aggressive natural history of aneurysms, will provide an opportunity for early diagnosis of those individuals at greatest risk, and could potentially lead to genetic therapies. Analysis of the Utah Population Database (UPDB) has shown that aneurysm has a strong familial component. This database, which combines a genealogy of Utah founders and their descendants with death certificates in the state since 1956 provides an excellent resource for ascertaining the extended high-risk families which will make gene localization possible. The goals of the proposal are to identify high-risk families, screen relatives of affected individuals using high resolution magnetic resonance angiography to detect aneurysms, collect blood samples for DNA from family members, characterize familial intracranial aneurysms and use a genome- wide search to identify susceptibility loci for familial intracranial aneurysms.
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