CCN1 Mutation is Associated with Atrial Septal Defect

Perrot, Andreas; Schmitt, Katharina; Roth, Eva-Maria G.; Stiller, Brigitte; Posch, Maximilian; Browne, Edmund; Timmann, Christian; Horstmann, Rolf D.; Berger, Felix; Özcelik, C.

doi:10.1007/s00246-014-1001-8

Cited by 20 publications

(14 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The human CYR61 gene encoding CCN1 was mapped to chromosome 1 at band p22.3 (Table 1 ) [ 26 , 27 ]. Genetic studies have suggested a relationship between a missense mutation of the CYR61 gene and patients with severe atrial septal defects [ 16 , 28 ]. The mutation leads to an exchange of residues with different properties in a highly conserved position in the N-terminal IGFBP module of CCN1.…”

Section: Introductionmentioning

confidence: 99%

Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities

2015

View full text Add to dashboard Cite

“CCN” is an acronym referring to the first letter of each of the first three members of this original group of mammalian functionally and phylogenetically distinct extracellular matrix (ECM) proteins [i.e., cysteine-rich 61 (CYR61), connective tissue growth factor (CTGF), and nephroblastoma-overexpressed (NOV)]. Although “CCN” genes are unlikely to have arisen from a common ancestral gene, their encoded proteins share multimodular structures in which most cysteine residues are strictly conserved in their positions within several structural motifs. The CCN genes can be subdivided into members developmentally indispensable for embryonic viability (e.g., CCN1, 2 and 5), each assuming unique tissue-specific functions, and members not essential for embryonic development (e.g., CCN3, 4 and 6), probably due to a balance of functional redundancy and specialization during evolution. The temporo-spatial regulation of the CCN genes and the structural information contained within the sequences of their encoded proteins reflect diversity in their context and tissue-specific functions. Genetic association studies and experimental anomalies, replicated in various animal models, have shown that altered CCN gene structure or expression is associated with “injury” stimuli—whether mechanical (e.g., trauma, shear stress) or chemical (e.g., ischemia, hyperglycemia, hyperlipidemia, inflammation). Consequently, increased organ-specific susceptibility to structural damages ensues. These data underscore the critical functions of CCN proteins in the dynamics of tissue repair and regeneration and in the compensatory responses preceding organ failure. A better understanding of the regulation and mode of action of each CCN member will be useful in developing specific gain- or loss-of-function strategies for therapeutic purposes.

show abstract

Section: Introductionmentioning

confidence: 99%

Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities

2015

View full text Add to dashboard Cite

show abstract

“…Variations in exons 2, 3, and 4 of the CYR61 gene are less frequently detected than in exon 5 in different types of patients (23)(24)(25). However, during our variation analysis, besides the detection of one missense variation in exon 2 (Arg47Trp), there was one silent variation in exon 3 (Lys152Lys), one missense variation in exon 4 (Phe213Leu), and two missense variations in exon 5 (Gly315Arg and Asp339Asn).…”

Section: Discussionmentioning

confidence: 57%

Identification of the cysteine-rich 61 (CYR61) gene variations in osteosarcoma patients

Hussain¹,

Ali²,

Singh³

et al. 2017

Turk J Med Sci

View full text Add to dashboard Cite

Background/aim: Osteosarcoma requires an angiogenesis process. CYR61 is one of the extracellular signaling molecules that promote angiogenesis, tumor growth, and the malignancy of osteosarcoma. In the present study, we investigate the CYR61 gene variations in osteosarcoma and their correlations with clinicopathological findings. Materials and methods:We performed variation analysis of the CYR61 gene in 58 patients with osteosarcoma. With an aim to ascertain the variety of variations in exons 2, 3, 4, and 5 of the CYR61 gene in osteosarcoma, we did a PCR-SSCP followed by DNA sequencing. Results:In osteosarcoma the CYR61 gene variations found were 18.96% (11/58) in exon 2, 3.44% (2/58) in exon 3, 8.62% (5/58) in exon 4, and 15.51% (9/58) in exon 5. In our variation analysis, we detected one missense variation in exon 2 (Arg47Trp), one silent variation in exon 3 (Lys152Lys), one missense variation in exon 4 (Phe213Leu), and two missense variations in exon 5 (Gly315Arg and Asp339Asn). The overall CYR61 variation frequency in exons 2, 3, 4, and 5 was determined to be 46.55% (27/58). Conclusion:Our study specifies the role of CYR61 gene variation in osteosarcoma. The result signifies that CYR61 might be used as a prognostic/diagnostic marker in osteosarcoma patients.

show abstract

“…Fold changes ≥ 2 or ≤ 0.5 are considered significant ADAMTS1 upregulation was shared by the two groups of patients. The secreted matricellular CYR61 protein was previously found highly expressed in remodeling atrial cardiomyocytes after myocardial infarction and proposed as an early prognostic biomarker of cardiac injury [89], while its mutations have been associated with ASD [90]. ADAMTS1 protein is a metalloprotease induced in the early phase of acute myocardial infarction playing an essential role in the repair of infarcted tissue and the development of heart fibrosis [91,92].…”

Section: Table 5 Relative Expression Of Genes Selectively Modulated Imentioning

confidence: 99%

Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

et al. 2020

View full text Add to dashboard Cite

Background: Tetralogy of Fallot (ToF) and Atrial Septal Defects (ASD) are the most common types of congenital heart diseases and a major cause of childhood morbidity and mortality. Cardiopulmonary bypass (CPB) is used during corrective cardiac surgery to support circulation and heart stabilization. However, this procedure triggers systemic inflammatory and stress response and consequent increased risk of postoperative complications. The aim of this study was to define the molecular bases of ToF and ASD pathogenesis and response to CPB and identify new potential biomarkers. Methods: Comparative transcriptome analysis of right atrium specimens collected from 10 ToF and 10 ASD patients was conducted before (Pre-CPB) and after (Post-CPB) corrective surgery. Total RNA isolated from each sample was individually hybridized on Affymetrix HG-U133 Plus Array Strips containing 38,500 unique human genes. Differences in the gene expression profiles and functional enrichment/network analyses were assessed using bioinformatic tools. qRT-PCR analysis was used to validate gene modulation. Results: Pre-CPB samples showed significant differential expression of a total of 72 genes, 28 of which were overexpressed in ToF and 44 in ASD. According to Gene Ontology annotation, the mostly enriched biological processes were represented by matrix organization and cell adhesion in ToF and by muscle development and contractility in ASD specimens. GSEA highlighted the specific enrichment of hypoxia gene sets in ToF samples, pointing to a role for hypoxia in disease pathogenesis. The post-CPB myocardium exhibited significant alterations in the expression profile

show abstract

CCN1 Mutation is Associated with Atrial Septal Defect

Cited by 20 publications

References 20 publications

Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities

Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities

Identification of the cysteine-rich 61 (CYR61) gene variations in osteosarcoma patients

Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

Contact Info

Product

Resources

About