Genetic Imbalance in Patients with Cervical Artery Dissection

Abstract

Background: Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) =1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107).Conclusion: The findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.

Familial aortic disease and a large duplication in chromosome 16p13.1

“…The pathogenicity of the MYH11 duplication in the presented family is not proven, in spite of suggestive evidence for an association of this duplication with arterial dissection (Kuang et al., ; Grond‐Ginsbach, Chen, et al., ). The observation that the duplication at 16p13.1 encompasses four ohnologs ( NDE1, MYH11, ABCC1, and ABCC6) further suggests its pathogenicity, because ohnologs were shown to be dose‐sensitive and overrepresented in pathogenic copy number variation (Makino & McLysaght, ; McLysaght et al., ; Tropeano et al., ).…”

“…K E Y W O R D S cosegregation, duplication 16p13.1, familial thoracic aortic aneurysm and dissection, whole exome sequencing 1 | BACKGROUND Large duplications of a region of chromosome 16p13.1 containing at least nine protein-coding genes (MPV17L, C16orf45, KIAA0430, NDE1, MYH11, C16orf63, ABCC1, ABCC6, NOMO3) occur in the European population at a low frequency of about 0.1% (Grozeva et al, 2012). Significant enrichment of 16p13.1 duplications was reported in patients with aortic dissections or with cervical artery dissections (Kuang et al, 2011;Grond-Ginsbach, Chen, et al, 2017), which suggests that carriers of the duplication have an increased risk for arterial dissection. However, in two pedigrees with familial thoracic aneurysms and dissections, the 16p13.1 duplication did not cosegregate with the aortic phenotype (Kuang et al, 2011).…”

Copy Number Variation and Risk of Stroke

“…42,43 Four further patients with CNV of the MYH11/ABCC6 locus were identified in a subsequent exploration of 833 CeAD patients. 12 This latter CNV-study of CeAD did not detect association with variation in a particular locus, but found association with variation in a predefined set of genes involved in cardiovascular system development.…”

Prognostic alternative splicing signature in cervical squamous cell carcinoma

“…Therefore, abnormal variations of splicing may induce the development of multiple diseases, including cancer. Recently, Pan et al and other groups revealed that the abnormal splicing of mRNA caused such diseases as inflammatory bowel disease, Alzheimer's disease, atherosclerosis disease [11][12][13][14][15]. Data from Lawes et al and other teams discovered that some tumours, e.g.…”