FAMILIAL CAVERNOUS MALFORMATIONS IN A LARGE FRENCH KINDRED - MAPPING OF THE GENE TO THE CCM1 LOCUS ON CHROMOSOME 7Q

Objectives-To characterise clinically a large French family affected w ith cerebral cavernomas and to check for linkage of this condition to chromosome 7. Methods-A family, originating from Normandy and in which five members had undergone surgery for cavernomas, was extended. All members older than 18 were studied clinically and by neuroimaging. Gen etic linkage analysis was conducted using 11 polymorphic microsatellit e markers located between D7S502 and D7S479. Results-The family includ ed three generations. Among the 25 members investigated, 11 had an abn ormal cerebral MRI, eight of them being symptomatic, and 12 were asymp tomatic with a normal MRI. The status of the two remaining members cou ld not be established on the basis of clinical and MRI data. The famil y reported shares some striking features with other previously linked families-namely, a high clinical penetrance and the presence of multip le lesions within most of the affected members. A lod score of 4.04 wa s obtained with marker D7S657 with no recombinant. Significant lod sco res were also obtained with D7S524 (Zmax=3.32 at theta=0.00) and D7S63 0 (Zmax=3.44 at theta=0.00). These results establish linkage of the co ndition found in this family to chromosome 7. Haplotype analysis stron gly suggests that the gene is telomeric to D7S802 and centromeric to D 7S479. Conclusions-These data confirm linkage of cerebral cavernous ma lformations to chromosome 7 in a non-Hispanic family.