on May 15, 2003
Published online before print May 15, 2003, doi: 10.1161/01.STR.0000072822.35605.8B
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Submitted on December 17, 2002
From the Center for Molecular Medicine and Genetics (S.W., M. van der V., H.K., G.T.) and Department of Surgery (H.K.), Wayne State University School of Medicine, Detroit, Mich; Department of Neurosurgery, University of Kuopio, Kuopio, Finland (A.R., K.H.); and Department of Neurosurgery, University of Helsinki, Helsinki, Finland (E.L., J.F., M.N., J.J., J.H.). * To whom correspondence should be addressed. E-mail: tromp{at}sanger.med.wayne.edu.
Background and Purpose--Genetic risk factors are considered important in the development, growth, and rupture of intracranial aneurysms; however, few have been identified. We analyzed intracranial aneurysm families with at least 2 affected persons and determined relationships between affected persons and assessed the inheritance patterns of aneurysms. Methods--Families with Results--We identified 346 Finnish multiplex families with 160 (46.2%) male and 186 (53.8%) female index cases. There were a total of 937 aneurysm cases, with an average of 2.7 cases per family. The majority of the families had only 2 affected relatives (n=206; 59.5%), although there were families with up to 6 (n=10), 7 (n=1), 8 (n=1), or 10 (n=2) affected persons. The affected relatives of the index cases included 108 sisters, 116 brothers, 105 parents, 30 children, 15 grandparents, 102 aunts or uncles, and 64 cousins. Of the 937 affected persons, 569 (60.7%) were alive and available for genetic analysis. Inheritance patterns consistent with autosomal recessiveness were observed in 198 (57.2%), autosomal dominance in 126 (36.4%), and autosomal dominance with incomplete penetrance in 19 (5.5%) of the families. Conclusions--The collection is the most extensive published to date and extends previous observations of familial aggregation that are consistent with a major gene effect.
Accepted on January 8, 2003
Familial Intracranial Aneurysms. An Analysis of 346 Multiplex Finnish Families
Shannon Wills BA;
2 members with verified diagnoses of intracranial aneurysms were recruited from Kuopio and Helsinki, Finland. Families with a diagnosis of other heritable disorders that have associated intracranial aneurysms, such as autosomal dominant polycystic kidney disease, were excluded.
Key words: genetics • pedigree • risk factors • stroke • subarachnoid hemorrhage
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