This Article Full Text Full Text (PDF) All Versions of this Article: 37/7/1697    most recent 01.STR.0000226624.93519.78v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wiest, T. Articles by Grond-Ginsbach, C. Search for Related Content PubMed PubMed Citation Articles by Wiest, T. Articles by Grond-Ginsbach, C. Pubmed/NCBI databases Medline Plus Health Information Connective Tissue Disorders Stroke Genetics Home Reference Related Collections Carotid and Vertebral A. Dissection Genetics of Stroke Genetics of cardiovascular disease

(Stroke. 2006;37:1697.)
© 2006 American Heart Association, Inc.

Original Contributions

Genetic Analysis of Familial Connective Tissue Alterations Associated With Cervical Artery Dissections Suggests Locus Heterogeneity

Tina Wiest, PhD; Sonja Hyrenbach, MD; Pinar Bambul, MD; Birgit Erker, MD; Alessandro Pezzini, MD; Ingrid Hausser, PhD; Marie-Luise Arnold, PhD; Juan José Martin, MD; Stefan Engelter, MD; Philippe Lyrer, MD; Otto Busse, MD; Tobias Brandt, MD Caspar Grond-Ginsbach, PhD

From the Department of Neurology (T.W., S.H., P.B., M.-L.A., T.B., C.G.-G.), University of Heidelberg, Germany; the Department of Neurology (B.E., O.B.), City Hospital Minden, Germany; the Department of Neurology (A.P.), University of Brescia, Italy; the Department of Dermatology (I.H.), University of Heidelberg, Germany; the Department of Neurology (J.J.M.), Sanatorio Allende, Cordoba, Argentina; the Neurological Clinic and Stroke Unit (S.E., P.L.), University Hospital Basel, Switzerland; and the Department of Neurological Rehabilitation (T.B.), Schmieder-Kliniken Heidelberg, Germany.

Correspondence to Dr Caspar Grond-Ginsbach, Neurology Department, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. E-mail Caspar_Grond-Ginsbach{at}med.uni-heidelberg.de

Background and Purpose— Cervical artery dissections (CAD) can be associated with connective tissue aberrations in skin biopsies. The analysis of healthy relatives of patients suggested that the connective tissue phenotype is familial with an autosomal dominant inheritance.

Methods— We performed genetic linkage studies in 3 families of patients with CAD. Connective tissue phenotypes for the patients and all family members were assessed by electron microscopic study of skin biopsies. A genome-wide linkage analysis of 1 family (1 patient with 8 healthy relatives) indicated 2 candidate loci. Three genes were subsequently studied by sequence analysis. Part of the genome was also studied by linkage analysis in 2 further families.

Results— The genome-wide scan in a single family suggested linkage between the hypothetical mutation causing the connective tissue phenotype and informative genetic markers on chromosome 15q24 (logarithm of the odds score: Z= +2.1). A second possible candidate locus (Z=+1.9) was found on chromosome 10q26. Sequence analysis of 3 candidate genes in the suggestive locus (chondroitin sulfate proteoglycan4 [CSPG4], lysyl oxidase-like1 [LOXL1] and fibroblast growth factor receptor2 [FGFR2]) did not lead to the identification of a mutation responsible for connective tissue alterations. In 2 additional smaller families the loci on chromosome 15q24 and 10q26 were excluded by linkage analysis.

Conclusions— Linkage analysis of a large family with CAD-associated connective tissue alterations suggested the presence of a candidate locus on chromosome 15q2 or on chromosome 10q26. Sequence analysis did not lead to the identification of a mutated candidate gene in 1 of these loci. The study of 2 additional pedigrees indicated locus heterogeneity for the connective tissue phenotype of CAD patients.

Key Words: cerebrovascular disorder • cervical artery dissection • genetic linkage analysis

This article has been cited by other articles:

				S. Debette and H. S. Markus The Genetics of Cervical Artery Dissection: A Systematic Review Stroke, June 1, 2009; 40(6): e459 - e466. [Abstract] [Full Text] [PDF]

				J. J. Martin, I. Hausser, P. Lyrer, O. Busse, R. Schwarz, R. Schneider, T. Brandt, M. Kloss, M. Schwaninger, S. Engelter, et al. Familial Cervical Artery Dissections: Clinical, Morphologic, and Genetic Studies Stroke, December 1, 2006; 37(12): 2924 - 2929. [Abstract] [Full Text] [PDF]