Mutations in the COL5A1 coding sequence are not common in patients with spontaneous cervical artery dissections

Background and Purpose-The dermal connective tissue of most patients with s pontaneous cervical artery dissections (sCAD) contains abnormal collagen fi bers. This suggests a predisposing connective tissue defect. The ultrastruc tural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patient s to mutations within the genes encoding type V collagen. The aim of this s tudy was to assess the alpha 1 chain of type V collagen (COL5A1) as a candi date gene for sCAD. Methods-We searched for mutations in the COL5A1 gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational pol ymorphism analysis and nucleotide sequence analysis of polymerase chain rea ction-amplified fragments of the whole COL5A1 coding sequence. Results-We detected 1 missense mutation leading to a predicted amino acid ( 192D/N) substitution within the N-terminal propeptide in 2 siblings. All ot her patients showed regular COL5A1 sequences with some silent polymorphisms . Conclusions-Mutations in the COL5A1 gene do not appear to be a major factor in the etiology of sCAD.