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on February 28, 2008

Stroke. 2008
Published online before print February 28, 2008, doi: 10.1161/STROKEAHA.107.495168
A more recent version of this article appeared on April 1, 2008
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Right arrow Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage
Right arrow Genetics of Stroke

Submitted on May 27, 2007
Revised on September 13, 2007
Accepted on September 19, 2007

Genomewide Linkage in a Large Dutch Family With Intracranial Aneurysms. Replication of 2 Loci for Intracranial Aneurysms to Chromosome 1p36.11-p36.13 and Xp22.2-p22.32

Ynte M. Ruigrok MD*; Cisca Wijmenga PhD; Gabriel J.E. Rinkel MD; Ruben van't Slot; Frank Baas MD; Marcel Wolfs BSc; Andries Westerveld PhD; and Yvo B.W.E.M. Roos MD

From the Department of Neurology (Y.M.R., G.J.E.R.), Rudolf Magnus Institute of Neuroscience and the Complex Genetics Section, Department of Biomedical Genetics (C.W., R.v.S., M.W.), University Medical Center Utrecht, Utrecht, The Netherlands; the Departments of Neurology (Y.M.R., Y.B.W.E.M.R.) and Human Genetics (F.B., A.W.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and the Department of Genetics (C.W.), University Medical Center Groningen, Groningen, The Netherlands.

* To whom correspondence should be addressed. E-mail: ij.m.ruigrok{at}umcutrecht.nl.

Background and Purpose—Approximately 2% of the general population harbor intracranial aneurysms. The prognosis after rupture of an intracranial aneurysm is poor; 50% of the patients die as a result of the rupture. Familial occurrence of intracranial aneurysms suggests there are genetic factors involved in the development of such aneurysms.

Methods—A large, consanguineous pedigree with 7 of 20 siblings affected by intracranial aneurysms was compiled and a genomewide linkage analysis on this family was performed using Illumina’s single nucleotide polymorphism-based linkage panel IV, which includes 5861 single nucleotide polymorphisms. A nonparametric linkage affecteds-only approach with GENEHUNTER was used.

Results—Two loci with suggestive linkage (nonparametric linkage=3.18) on chromosome regions 1p36 and Xp22 were identified. Additional microsatellite markers were genotyped in the 2 candidate loci and showed suggestive linkage to the locus on chromosome 1 with a nonparametric linkage of 3.18 at 1p36.11-p36.13 and significant linkage to the locus on chromosome X with a nonparametric linkage of 4.54 at Xp22.2-p22.32.

Conclusions—The 2 potential loci for intracranial aneurysms, which we identified in this large Dutch family, overlap with loci that have already been identified in previous linkage studies from different populations. Identification of genes from these loci will be important for a better understanding of the disease pathogenesis.


Key words: aneurysm • genetics • subarachnoid hemorrhage




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[Abstract] [Full Text] [PDF]