Exclusion of mutations in the gene for type III collagen (COL3A1) as a common cause of intracranial aneurysms or cervical artery dissections

Kuivaniemi, Helena; Prockop, Darwin J.; Wu, Yanan; Madhatheri, S; Kleinert, Caren; Earley, James J.; Jokinen, A.; Stolle, Catherine A.; Majamaa, Kari; Myllylä, V.V.; Norrgård, Örjan; Schievink, Wouter I.; Mokri, Bahram; Fukawa, Osamu; Berg, J. W. M. ter; Paepe, Anne De; Lozano, Andrés M.; Leblanc, Richard; Ryynänen, Markku; Baxter, B. Timothy; Shikata, Hiromasa; Ferrell, Robert E.; Tromp, Gerard

doi:10.1212/wnl.43.12.2652

Cited by 131 publications

(54 citation statements)

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“…2 This type of mutation (glycine substitutions in triple helical region of COL3A1) is typical for EDS-IV, but was not found in CAD patients without clinical signs of vascular EDS. 14,30 Our findings in family I suggested that a patient with familial CAD might be affected with mild and otherwise unrecognized forms of vascular EDS.…”

Section: Martin Et Al Familial Cervical Artery Dissections 2927mentioning

confidence: 81%

Familial Cervical Artery Dissections

Martin

Haußer

Lyrer

et al. 2006

Stroke

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Background and Purpose-Genetic risk factors are thought to play a role in the etiology of spontaneous cervical artery dissections (CAD). However, familial CAD is extremely rare. In this study we analyzed patients with familial CAD and asked the question whether familial CAD has particular features. Methods-Seven families with 15 CAD patients were recruited. All patients were carefully investigated by a neurologist, a neuroradiologist, and a dermatologist for clinical characteristics. From 11 patients a skin biopsy was performed to study the morphology of the connective tissue and to analyze the coding sequences of COL3A1, COL5A1, COL5A2, and part of COL1A1. Results-The mean age of the patients (nϭ15, 9 women) at their first dissection was 36.2 years (median age 32 years, range 18 to 59). Two patients had bilateral CAD. One patient had a right and a left internal carotid artery dissection in successive weeks, another patient had 5 dissections over a period of 8 years. A high intrafamilial correlation was found between the affected vessels (ie, the carotid and the vertebral arteries) and between ages at the first dissection. In 1 patient we found clear and reproducible ultrastructural abnormalities in the skin biopsy, but the second patient from the family was not studied, because he died as a result of CAD before this study. The dermal connective tissue aberrations in the examined patient were similar to mild findings in patients with vascular Ehlers-Danlos syndrome (EDS type IV), but might be iatrogenic and related to long-term corticosteroid inhalation therapy. All other analyzed patients showed normal connective tissue morphology. In patients from 6 families we analyzed the whole coding sequence of COL3A1, COL5A1, and COL5A2, and from part of COL1A1. A missense mutation in the COL3A1 gene (leading to a G157S substitution in type III procollagen) was detected in both patients from 1e family. Two patients from another family carried a rare nonsynonymous coding polymorphism in COL5A1 (D192N); 1 of them carried also a rare variant in COL5A2 (T12337). Conclusions-Familial CAD patients are young and probably are at high risk for recurrent or multiple CAD.Ultrastructural alterations of the dermal connective tissue might not be an important risk factor for familial CAD. However, the finding of a COL3A1 mutation revealed the presence of an inherited connective tissue disorder in 1 family.

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Section: Martin Et Al Familial Cervical Artery Dissections 2927mentioning

confidence: 81%

Familial Cervical Artery Dissections

Martin

Haußer

Lyrer

et al. 2006

Stroke

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“…34,35 There is also accumulating evidence indicating that overdegradation of vascular structural proteins by proteinases is an important mechanism involved in the development and rupture of aneurysms. 7 The present study sought to ascertain whether polymorphisms in MMP genes influence the susceptibility of intracranial aneurysms.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in Matrix Metalloproteinase-1, -3, -9, and -12 Genes in Relation to Subarachnoid Hemorrhage

Zhang

Dhillon

Geary

et al. 2001

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Background and Purpose-Intracranial aneurysm, which underlies the vast majority of subarachnoid hemorrhage incidences, has a multifactorial etiology, and the importance of genetic factors is increasingly recognized. Development and rupture of intracranial aneurysms involve degradation and remodeling of the vascular wall matrix in which the matrix metalloproteinases (MMPs) play an important role. The possible impact of MMP gene polymorphisms on susceptibility to intracranial aneurysms is still controversial, with conflicting data from different reported studies. Methods-In this study we analyzed 5 different functional promoter polymorphisms in the MMP-1, MMP-3, MMP-9, and MMP-12 genes in a sample of 92 patients with aneurysmal subarachnoid hemorrhage and 158 healthy control subjects, all from southern England. Results-No significant difference was detected between the patient and control groups in genotype distribution of any of the polymorphisms studied. Conclusions-The

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“…17,18 Analyses of the connective tissue in walls of IA documented anomalies in the type III collagen network 19 -22 but found no mutations in the COL3A1 gene itself. 23,24 Although IA families have been collected in several countries, a sufficient number of large pedigrees for classical linkage studies has not been recruited so far. Recently, 83 affected Japanese sib pairs were genotyped with microsatellite polymorphisms at 404 chromosomal loci by Onda et al 25 They found 3 suggestive linkages for IA on chromosomes 5q22 to 31, 14q22, and-with the highest logarithm of odds score-7q11.…”

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confidence: 99%