Genetic Profile in Patients With Aortic Syndrome


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

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: March 30, 2022

Detailed Description

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.


  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • % of patients with presence of Missense mutations
    • Time Frame: post-treatment
    • massive sequencing
  • % of patients with presence of splicing mutations
    • Time Frame: post-treatment
    • massive sequencing
  • % of patients with presence of frameshift mutations
    • Time Frame: post-treatment
    • massive sequencing
  • % of patients with presence of nonframeshift mutations
    • Time Frame: post-treatment
    • massive sequencing

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 16 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Hospitales Universitarios Virgen del Rocío
  • Provider of Information About this Clinical Study
    • Principal Investigator: Antonio M. Puppo Moreno, Principal Investigator – Hospitales Universitarios Virgen del Rocío
  • Overall Official(s)
    • Antonio M Puppo Moreno, MD;PhD, Principal Investigator, Andaluz Health Service


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