A new locus for autosomal dominant intracranial aneurysm, ANIB4, maps to chromosome 5p15.2-14.3

• Published in: Journal of medical genetics Vol. 43; no. 6; p. e31
• Main Authors: Verlaan, D J, Dubé, M-P, St-Onge, J, Noreau, A, Roussel, J, Satgé, N, Wallace, M C, Rouleau, G A
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-06-2006; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adult; Alleles; Aneurysms; Chromosome Mapping; Chromosomes, Human, Pair 5; DNA Mutational Analysis; Electronic Letter; Family medical history; Female; French Canadian; Genes; Genes, Dominant; Genetic Linkage; Genetic Predisposition to Disease; genome-wide scan; Genomes; Haplotypes; heterogeneity score; HLOD; Humans; intracranial aneurysm; Intracranial Aneurysm - diagnosis; Intracranial Aneurysm - genetics; intracranial aneurysms; locus; magnetic resonance angiography; Male; Middle Aged; MRA; Pedigree; Proteins; SAH; Smoking; Studies; subarachnoid haemorrhage
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.033209

Background: Intracranial aneurysms (IA) are dilatations of intracranial arteries that occur most commonly at arterial bifurcations. Unruptured IA are present in approximately 1–2% of the population aged over 30 years of age. Aneurysms are only rarely symptomatic unless they rupture, which typically results in a subarachnoid haemorrhage associated with high morbidity and mortality. Methods: A large French Canadian (FC) family (Aneu60) was identified which contained 12 affected individuals with intracranial aneurysms. Nine of the affected patients and three unaffected individuals were sent for an 8 cM genome-wide scan. Multipoint and two-point methods were used to analyse the scan data by using a dominant parametric model. Results: We identified an IA susceptibility locus (ANIB4) located on chromosome 5p15.2-14.3. The locus was found by genome-wide linkage analysis and follow up analyses provided a maximum multipoint LOD score of 3.57 over the region. An identical haplotype segment of 7.2 Mb was found in a second FC pedigree and contributes to the refinement of the candidate gene interval. Conclusions: Our results indicate that there is a major gene locus on chromosome 5p.