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PERSPECTIVE article

Front. Cardiovasc. Med.
Sec. Coronary Artery Disease
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1486273
This article is part of the Research Topic Spontaneous Coronary Artery Dissection: Pathology and Pathophysiology View all 3 articles

GENETICS ARCHITECTURE OF SPONTANEOUS CORONARY ARTERY DISSECTION IN AN ITALIAN COHORT

Provisionally accepted
Marta Casula Marta Casula 1,2Daniela Marchetti Daniela Marchetti 3Lucia Trevisan Lucia Trevisan 4*Laura Pezzoli Laura Pezzoli 3Matteo Bellini Matteo Bellini 3Serena Patrone Serena Patrone 5Antonio Zingarelli Antonio Zingarelli 4Fabio Gotta Fabio Gotta 4Maria Iascone Maria Iascone 3Paola Mandich Paola Mandich 1,4,5
  • 1 University of Genoa, Genoa, Italy
  • 2 University of Sassari, Sassari, Sardegna, Italy
  • 3 Laboratory of Medical Genetics, ASST Papa Giovanni XXIII, Bergamo, Italy, Bergamo, Lombardy, Italy
  • 4 San Martino Hospital (IRCCS), Genova, Liguria, Italy
  • 5 Unit of Neurorehabilitation Clinic, Department of Neuroscience, San Martino Hospital (IRCCS), Genoa, Italy

The final, formatted version of the article will be published soon.

    Spontaneous coronary artery dissection (SCAD) is a relevant non-atherosclerotic cause of acute coronary syndrome with a complex genetic architecture. Recent discoveries have highlighted the potential role of miRNAs and protein-coding genes involved in the processing of small RNAs in the pathogenesis of SCAD. Furthermore, there may be a connection between SCAD and the increased cardiovascular risk observed in fragile X premutation carriers as well as a correlation with pathogenetic variants in genes encoding for collagen and extracellular matrix which are related to connective tissue disorders (CTDs). In our cohort of 15 Italian SCAD-patients, a total of 37 rare variants were identified in 34 genes by whole exome sequencing (WES) and TRIO-WES analysis when both parents were available. 3 Likely Pathogenic/Pathogenetic (LP/P) variants were found in genes previously associated with SCAD and CTDs (COL3A1, COL1A2, SMAD3) and 26 variants of uncertain significance (VUS) in genes previously associated with SCAD and CTDs. TRIO-WES analysis revealed 7 de novo variants, one of which was found in a potential novel candidate gene (DROSHA). Additionally, a premutation allele of 55±2 CGG repeats in the promoter of the FMR1 gene was identified in two related SCAD patients by test for CGG-repeat expansions in the 5’-UTR of the FMR1 gene. Our findings suggest various potential mechanisms such as mRNA toxicity, miRNA regulation, alteration of collagen and the extracellular matrix architecture, all of which could disrupt vascular homeostasis and finally, WES and TRIO-WES have proven to be the most powerful approaches for characterizing the genetic background of SCAD.

    Keywords: WES - whole-exome sequencing, Drosha, Connective tissue disorder, miRNA, Spontaneous coronary artery dissection (SCAD)

    Received: 25 Aug 2024; Accepted: 01 Nov 2024.

    Copyright: © 2024 Casula, Marchetti, Trevisan, Pezzoli, Bellini, Patrone, Zingarelli, Gotta, Iascone and Mandich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lucia Trevisan, San Martino Hospital (IRCCS), Genova, 16132, Liguria, Italy

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