A new locus for autosomal dominant intracranial aneurysm, ANIB4, maps to chromosome 5p15.2-14.3.
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.
Verlaan
D J
DJ
Dubé
M-P
MP
St-Onge
J
J
Noreau
A
A
Roussel
J
J
Satgé
N
N
Wallace
M C
MC
Rouleau
G A
GA
D000328:Adult; D000483:Alleles; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D002532:Intracranial Aneurysm / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012907:Smoking