Genetic Profile in Patients With Aortic Syndrome

Gene Abnormality Clinical Trial

— GEN-AOR  

Official title:

Genetic Profile in Patients With Aortic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04751058
• Other study ID #: HU Virgen Rocio
• Status: Completed
• Start date: February 27, 2021
• Est. completion date: March 30, 2022

Study information

• Verified date: April 2022
• Source: Hospitales Universitarios Virgen del Rocío
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: March 30, 2022
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Aortic Syndrome
• Gene Abnormality
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Andalucia
Spain	Hospital Universitario Virgen del Rocio	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Hospitales Universitarios Virgen del Rocío

Country where clinical trial is conducted

Spain, 

References & Publications (21)

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	% of patients with presence of Missense mutations	massive sequencing	post-treatment
Primary	% of patients with presence of splicing mutations	massive sequencing	post-treatment
Primary	% of patients with presence of frameshift mutations	massive sequencing	post-treatment
Primary	% of patients with presence of nonframeshift mutations	massive sequencing	post-treatment