Published Online
on March 20, 2003

A more recent version of this article appeared on April 1, 2003

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Submitted on September 25, 2002
Accepted on October 2, 2002

Absence of Linkage of Familial Intracranial Aneurysms to 7q11 in Highly Aggregated Japanese Families

Shigeki Yamada MD; Maki Utsunomiya MPH; Kayoko Inoue MD, MPH; Kazuhiko Nozaki MD, PhD; Susumu Miyamoto MD, PhD; Nobuo Hashimoto MD, PhD; Katsunobu Takenaka MD, PhD; Takeo Yoshinaga PhD; and Akio Koizumi MD, PhD^*

From the Departments of Neurosurgery (S.Y., K.N., S.M., N.H.) and Health and Environmental Sciences (M.U., K.I., T.Y., A.K.), Kyoto University Graduate School of Medicine, Kyoto; and Department of Neurosurgery, Takayama Red Cross Hospital, Gifu (K.T.), Japan.

^* To whom correspondence should be addressed. E-mail: koizumi{at}pbh.med.kyoto-u.ac.jp.

Background and Purpose--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 (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.

Key words: aneurysm, intracranial • elastin • genetics

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