Whole Exome Sequencing in Coronary Artery Ectasia

Study Overview
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Brief Summary
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The goal of this observational study is to assess the role of the whole exome sequencing (WES) application in patients with giant coronary artery ectasia (CAE) with a high-risk of genetic background. The main question it aims to answer are: the assessment of role of WES in CAE the detection of novel pathogenic mutations associated with CAE development

Detailed Description
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Coronary artery aneurysm and ectasia (CAAE) is defined as a dilation of the coronary artery by at least 1.5 times compared to the adjacent segment. The incidence of CAAE is reported in 0.3-5.3% of patients undergoing coronary angiography. Giant CAAE is a rare phenomenon characterized by a dilation of a coronary artery exceeding 2 to 4 centimeters and it was found only in 0.02% of patients undergoing coronary angiography. The most common etiology of CAAE is atherosclerosis, followed by Kawasaki disease, infectious septic emboli, connective tissue disease and arteritis. Iatrogenic causes are less common. There are few genetic reports on potential loci associated with CAAE. Meta-analysis of genome wide association studies performed in European and Japanese population of children with Kawasaki disease has identified ITPKC, FCGR2A, CASP3 and FAM167A genomic regions to be associated with susceptibility to develop CAAE. Furthermore, 9p21 variant has been linked with coexistence of coronary artery disease, cerebral artery aneurysms and aortic aneurysms, mainly due to suspected potential adverse vascular remodeling. Nevertheless, the direct association of specific genetic variants with CAAE formation, especially with those giants, has not been proven. Therefore, the investigators aim to assess the role of the whole exome sequencing (WES) application in patients with giant coronary artery ectasia (CAE) with a high-risk of genetic background.

Official Title
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Genetic Background Assessment With Whole Exome Sequencing in a Giant Coronary Artery Ectasia: a Pilot Study.

Conditions
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Coronary Ectasia, Coronary Aneurysm

Intervention / Treatment
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* Diagnostic Test: Whole exome sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed giant coronary artery aneurysm and ectasia (CAAE) high risk of genetic background Exclusion Criteria: the lack of informed consent for whole exome sequencing (WES) analysis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Proband<br>Patient with extremely giant coronary artery ectasia (CAE) and positive family history | Diagnostic Test: Whole exome sequencing<br>* Bioinformatic analysis of raw WES data and variants prioritization were performed as previously described. Reads were aligned to the hg38 reference genome sequence and visualized by Integrative Genomic Viewer.<br>* Other names: Genetic analysis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The novel pathogenic mutations associated with CAE development | Reads of WES will be aligned to the hg38 reference genome sequence and visualized by Integrative Genomic Viewer. | Until June 11, 2023 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary ectasia, Coronary aneurysm, Whole exome sequencing, Mutations