Genetic Profile in Patients With Aortic Syndrome

Study Overview
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Brief Summary
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The overall prevalence has increased significantly in the general population, which may be due in part to advances in diagnostic techniques, such as improved imaging techniques. Aortic dissection (AD) can cause sudden cardiac death (SCD). Approximately 95% of thoracic AAS are clinically silent until a life-threatening complication arises in an unpredictable manner and presents as sudden cardiac death. The peak incidence of death caused by aortic dissection occurs within 48 hours, therefore, timely diagnosis is essential and saves lives. We have traditionally associated as risk factors in patients with ASA long-term arterial hypertension, present in 66-75% of cases, smoking, dyslipidemia or atherosclerotic disease. Likewise, any condition that alters the structure of the aorta such as: collagen diseases, aneurysms, bicuspid aorta, and manipulation of the thoracic aorta (cardiac surgery, 18%, or percutaneous intervention that can injure the intima) is involved in ASA. In addition to the well-known hereditary syndromes that affect collagen (Marfan, Elher-Danlos ...) there is a clear familial aggregation: 13-19% of patients without identifiable syndrome have first-degree relatives with thoracic aortic aneurysms or ICD, something that has been called thoracic aortic dissection and familial aneurysm syndrome. Notable achievements have been made in the discovery of genetic mutations associated with SAA and key regulatory molecules involved, including the extracellular matrix (ECM), cytoskeletal proteins, and the TGF-β signaling pathway. Identification of the causative gene is advantageous for both patients and their families, especially those who do not show symptoms. The specific underlying genotype could benefit the process of diagnosis, surveillance and surgery, with the aim of reducing morbidity and mortality

Detailed Description
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HYPOTHESIS.: A proportion of patients admitted to the Hospital with a diagnosis of Aortic Syndrome without phenotypic characteristics are carriers of mutations. The presence of these mutations can condition both the indication for treatment, post-surgical aortic remodeling, and family traceability. OBJECTIVE.: The objective of this study is to analyze the prevalence of mutations in non-phenotypic patients admitted urgently due to Aortic Syndrome. Material and method: Patients admitted to the Intensive Care Unit of the Virgen del Rocio University Hospital in Seville (third level Hospital) with the diagnosis of Aortic Syndrome will be included. The clinical and angiographic variables were analyzed. All patients will undergo, with prior informed consent, a peripheral blood extraction, from which a DNA sample will be obtained using the ChemagicTM 360 equipment. This DNA will be processed for massive sequencing on Illumina's NextSeq500 platform using the technology Capture SeqCap EZ Choice Library NimbleGen. The data generated will be analyzed bioinformatically and the identified variants prioritized based on their population frequency (<0.01), location (exonic and close to splicing sites), their presence in databases of clinical significance ClinVar, HGMD and LOVD and the phenotypic association of the mutated gene OMIM and Orphanet.

Official Title
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Genetic Profile in Patients With Aortic Syndrome

Conditions
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Gene Abnormality, Acute Aortic Syndrome

Intervention / Treatment
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* Genetic: genetic analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient older than 16 years Patients admitted alive with a diagnosis of acute aortic syndrome Written consent to be DNA analysis and conservation in the DNA bank Exclusion Criteria: Refusal to participate in the study and , or analysis of their DNA. Without life expectancy and , or Income without life.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: genetic analysis|Intervention details: sampling in peripheral blood for the Methodology: Automatic DNA extraction (ChemagicTM 360) Mass sequencing using SeqCap EZ Choice Library capture technology (NimbleGen) and NextSeq sequencer (Illumina). Bioinformatic analysis:. Identification of point mutations and small deletions or insertions Analysis of CNVs using the BEDtools program package Search of the identified variants in the following public databases: 1000G, dbSNP, ExAC, EVS, GenomADm CSVS and DGV. Those with a MAF> 1% have been considered benign, in public or private databases of our population. The analysis process has focused exclusively on the genes described to date as associated with the pathology under study and included in the panel used. The reference sequences used for these genes are: determination of possible mutations, nucleotics, etc.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of patients with presence of Missense mutations | massive sequencing | post-treatment | 
| % of patients with presence of splicing mutations | massive sequencing | post-treatment | 
| % of patients with presence of frameshift mutations | massive sequencing | post-treatment | 
| % of patients with presence of nonframeshift mutations | massive sequencing | post-treatment |