Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families.
OBJECTIVE
We sought to test the linkage of familial intracranial aneurysms (FIAs) to the ELN (elastin) locus in chromosome 7q11 reported previously.


METHODS
Intracranial aneurysm (IA) probands were searched from patient records or neurosurgeons' recalls in collaborating hospitals. Members of the participating probands' families who had unknown affection status were screened by MR angiography and diagnosed by digital subtraction angiography. Inclusion criteria of families for genetic analyses were as follows: at least 3 alive affected members or 2 alive affected members with at least 1 unaffected member (>or=60 years). Linkage to the ELN locus was tested with the use of GENEHUNTER by parametric and nonparametric methods. To exclude false-negatives in the linkage analysis, the lowest 5% limits of logarithms of the odds (LOD) and nonparametric LOD (NPL) scores for individual families and for the total set of families were simulated on assumption that the ELN locus is linked to FIAs.


RESULTS
Questionnaires were sent to 885 patients, and 563 responded. Seventy-nine probands were positive for family history. One hundred thirty-four family members of unknown affection status were screened. A total of 14 families with 64 members met the criteria. Linkage to the ELN locus was discarded in 11 families and was inconclusive for 3 families. The total LOD and total NPL scores for 14 families were -8.04 and -0.643, respectively. Our conclusion did not change even when the values of penetrance were changed or only affected members were analyzed.


CONCLUSIONS
The majority of aggregated IA Japanese families may not have a genetic linkage to chromosome 7q11.
Yamada
Shigeki
S
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Japan.
Utsunomiya
Maki
M
Inoue
Kayoko
K
Nozaki
Kazuhiko
K
Miyamoto
Susumu
S
Hashimoto
Nobuo
N
Takenaka
Katsunobu
K
Yoshinaga
Takeo
T
Koizumi
Akio
A
D000328:Adult; D002897:Chromosomes, Human, Pair 7; D004549:Elastin / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D002532:Intracranial Aneurysm / Q000175:diagnosis / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010375:Pedigree
D004549:Elastin