Cavernous angiomas are vascular malformations mostly located in the central
nervous system and characterized by enlarged capillary cavities without in
tervening brain parenchyma(1). Clinical symptoms include seizures, haemorrh
age and focal neurological deficits. Cavernous angiomas prevalence is close
to 0.5% in the general population(2). They may be inherited as an autosoma
l dominant condition in as much as 50% of cases(3). Cerebral cavernous malf
ormations (CCM) loci were previously identified on 7q, 7p and 3q (refs 4,5)
. A strong founder effect was observed in the Hispano-American population,
all families being linked to CCM1 on 7q (refs 4,6,7). CCM1 locus assignment
was refined to a 4-cM interval bracketed by D7S2410 and D7S689 (ref. 8). H
ere we report a physical and transcriptional map of this interval and that
CCM1, a gene whose protein product, KRIT1, interacts with RAP1A (also known
as KREV1; ref. 9), a member of the RAS family of GTPases, is mutated in CC
M1 families. Our data suggest the involvement of the RAP1A signal transduct
ion pathway in vasculogenesis or angiogenesis(10).