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(Stroke. 1999;30:1628-1631.)
© 1999 American Heart Association, Inc.

Original Contributions

Type III Collagen Deficiency in Saccular Intracranial Aneurysms

Defect in Gene Regulation?

J. S. P. van den Berg, MD; G. Pals, PhD; F. Arwert, PhD; R. C. M. Hennekam, MD; K. W. Albrecht, MD; A. Westerveld, PhD M. Limburg, MD

From the Departments of Neurology (J.S.P. van den B., M.L.), Pediatrics (R.C.M.H.), and Neurosurgery (K.W.A.) and Institute for Human Genetics (R.C.M.H., A.W.), University of Amsterdam, Academic Medical Center; Department of Human Genetics, Vrije Universiteit, Amsterdam (G.P., F.A.); and Department of Neurology, University of Nijmegen, University Hospital Nijmegen (J.S.P. van den B.) (Netherlands).

Correspondence to J.S.P. van den Berg, Department of Neurology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands. E-mail J.vandenberg{at}czzoneu.azn.nl

Background and Purpose—We sought to determine whether there are mutations in the COL3A1 gene in patients with saccular intracranial aneurysms with a type III collagen deficiency and whether there is an association between a marker in the COL3A1 gene and saccular intracranial aneurysms. One of the heritable factors possibly involved in the pathogenesis of saccular intracranial aneurysms is a reduced production of type III collagen, demonstrated earlier 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 reduced production of type III collagen in cultured diploid fibroblasts from a skin biopsy.

Results—No mutations could be demonstrated in the COL3A1 gene, especially not 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 production. No differences were found between 41 patients and 41 controls in allele frequencies of a DNA tandem repeat polymorphism located in the COL3A1 gene.

Conclusions—It is concluded that the COL3A1 gene is not directly involved in 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 further exploration.

Key Words: cerebral aneurysm • collagen • pathology

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