EXCLUSION OF MUTATIONS IN THE GENE FOR TYPE-III COLLAGEN (COL3A1) AS A COMMON-CAUSE OF INTRACRANIAL ANEURYSMS OR CERVICAL ARTERY DISSECTIONS - RESULTS FROM SEQUENCE-ANALYSIS OF THE CODING SEQUENCES OF TYPE-IIICOLLAGEN FROM 55 UNRELATED PATIENTS

We performed detailed DNA sequencing analysis on type III collagen cDN A from 58 patients with either intracranial artery aneurysms or cervic al artery dissections. The 58 patients were of seven different nationa lities; among the patients were three pairs of relatives, so that 55 w ere unrelated, and of these, 29 had at least one blood relative with e ither an intracranial artery aneurysm or a cervical artery dissection. The age of the patients at the time of diagnosis ranged from 15 to 68 years (mean +/- SD = 40.3 +/- 11.0). The study group consisted of 25 males and 33 females. The analysis covered 3,232 nucleotides of signif icant (nonredundant) sequences per allele; therefore, we analyzed as m any as 355,520 nucleotides. Mutations in the coding sequences for the triple-helical domain of type III collagen were excluded in 40 individ uals with intracranial aneurysms and 18 individuals with cervical arte ry dissections. Direct sequencing of polymerase chain reaction product s allowed mutations to be excluded with a high degree of confidence. M utations that markedly decreased expression from one allele were also excluded in 42 of the 58 individuals, since,the presence of both bases at one or more polymorphic sites in the 42 patients showed that two a lleles were transcribed. The results indicated that mutations in the g ene for type III procollagen (COL3A1) are not a common cause of either intracranial artery aneurysms or cervical artery dissections.