Type III collagen deficiency in saccular intracranial aneurysms - Defect in gene regulation?

Background and Purpose-We sought to determine whether there are mutations i n the COL3A1 gene in patients with saccular intracranial aneurysms with a t ype III collagen deficiency and whether there is an association between a m arker in the COL3A1 gene and saccular intracranial aneurysms. One of the he ritable factors possibly involved in the pathogenesis of saccular intracran ial aneurysms is a reduced production of type III collagen, demonstrated ea rlier by protein studies. Methods-We analyzed the type III collagen gene in a group of 41 consecutive patients with an intracranial aneurysm, of whom 6 patients had shown a red uced production of type III collagen in cultured diploid fibroblasts from a skin biopsy. Results-No mutations could be demonstrated in the COL3A1 gene, especially n ot in the globular N- and C-terminal regions. A null allele was excluded in 25 patients, including 1 patient with a decreased type III collagen produc tion. No differences were found between 41 patients and 41 controls in alle le frequencies of a DNA tandem repeat polymorphism located in the COL3A1 ge ne. Conclusions-It is concluded that the COL3A1 gene is not directly involved i n the pathogenesis of most of intracranial aneurysms. The reduced type III collagen production in cultured fibroblasts found in some patients with an intracranial aneurysm is not explained by the present study and needs furth er exploration.