Familial cavernous malformations in a large French kindred:mapping of the gene to the CCM1 locus on chromosome 7q

OBJECTIVES—To characterise clinically a largeFrench family affected with cerebral cavernomas and to check forlinkage of this condition to chromosome 7.
METHODS—A family, originating from Normandy andin which five members had undergone surgery for cavernomas, wasextended. All members older than 18 were studied clinically and byneuroimaging. Genetic linkage analysis was conducted using 11 polymorphic microsatellite markers located between D7S502 and D7S479.
RESULTS—The family included three generations.Among the 25 members investigated, 11 had an abnormal cerebral MRI,eight of them being symptomatic, and 12 were asymptomatic with a normalMRI. The status of the two remaining members could not be establishedon the basis of clinical and MRI data. The family reported shares somestriking features with other previously linked families—namely, a high clinical penetrance and the presence of multiple lesions within most ofthe affected members. A lod score of 4.04 was obtained with markerD7S657 with no recombinant. Significant lod scores were also obtainedwith D7S524 (Zmax=3.32 at θ=0.00) and D7S630 (Zmax=3.44 at θ=0.00).These results establish linkage of the condition found in this familyto chromosome 7. Haplotype analysis strongly suggests that the gene istelomeric to D7S802 and centromeric to D7S479.
CONCLUSIONS—These data confirm linkage ofcerebral cavernous malformations to chromosome 7 in a non-Hispanic family.