Copy number variation in patients with cervical artery dissection
Caspar Grond-Ginsbach1, Bowang Chen, Rastislav Pjontek
1Department of Neurology, University of Heidelberg, Heidelberg, Germany. Caspar.Grond-Ginsbach@med.uni-heidelberg.de
European Journal of Human Genetics : EJHG
|May 24, 2012
Summary
Rare genetic variants, specifically copy number variants (CNVs), may predispose individuals to cervical artery dissection (CeAD), particularly those with connective tissue abnormalities. This study identified specific CNVs linked to CeAD pathogenesis.
Area of Science:
- Genetics and Molecular Biology
- Neurology
- Vascular Biology
Background:
- Cervical artery dissection (CeAD) is a significant cause of ischemic stroke in young, healthy individuals.
- Microscopic alterations in dermal connective tissue are observed in many CeAD patients, suggesting a potential underlying genetic predisposition.
- The role of rare genetic variations, such as copy number variants (CNVs), in CeAD pathogenesis remains underexplored.
Purpose of the Study:
- To investigate the association of rare genetic deletions and duplications (CNVs) with cervical artery dissection (CeAD).
- To identify specific genes and biological pathways implicated in CeAD pathogenesis, especially in patients with connective tissue abnormalities.
Main Methods:
- Analysis of 49 CeAD patients with electron microscopic (EM) connective tissue alterations (EM+) and 21 CeAD patients with normal connective tissue (EM-).
- Screening for copy number variants (CNVs) using Affymetrix 6.0 microarrays, comparing patient data against control cohorts (403 controls, 2402 disease-free individuals).
- Utilizing Gene Ontology (GO) Term Mapper to analyze the genetic content of identified CNVs and assess associations with biological processes.
Main Results:
- Thirteen CeAD-associated CNVs, encompassing 83 protein-coding genes, were identified in EM+ patients.
- Five CeAD-associated CNVs, containing nine genes, were found in EM- patients, indicating a lower gene density compared to EM+ patients (Mann-Whitney P=0.039).
- Enrichment analysis revealed CeAD-associated CNVs were significantly involved in extracellular matrix organization (e.g., COL5A2, COL3A1) and collagen fibril organization (P=0.0001), with a potential link to TGF-beta receptor signaling.
Conclusions:
- Rare genetic variants, particularly CNVs, likely contribute to the pathogenesis of cervical artery dissection.
- Patients with microscopic connective tissue abnormalities exhibit a distinct pattern of CeAD-associated CNVs.
- The identified genes involved in extracellular matrix and collagen organization highlight potential molecular mechanisms underlying CeAD.
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