Poster Presentation 40th Annual Lorne Genome Conference 2019

The Intercellular Tight Junction and Spontaneous Coronary Artery Dissection. (#124)

James K Fahey 1 , Sarah Williams 2 , Sonika Tyagi 2 , David Powell 2 , Jeannette Hallab 3 , Gulrez Chahal 3 , Mirana SM Ramialison 3 , Anthony J White 1
  1. Faculty of Medicine, Nursing and Health Sciences Monash University, School of Clinical Sciences at Monash Health, Melbourne, VIC, Australia
  2. Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia
  3. ARMI, Monash University, Clayton, VIC, Australia

Spontaneous coronary artery dissection (SCAD) is a clinical event, affecting female patients almost exclusively, in which intramural hematoma develops in a coronary artery and manifests as acute coronary syndrome. Although most cases of SCAD are known to have a sporadic occurrence, we identified a mother and daughter who had SCAD of the left anterior descending coronary artery at age 52 and 40 years. To identify the genetic cause of the disease, whole genome sequencing was performed on their blood samples. The downstream bioinformatics analysis identified F11R gene as a priority gene candidate with 175C>G (rs753577357) variant in both mother and daughter. The 3-dimensional structure of the F11R protein reveals homodimerization through one of the immunoglobulin-like domains, with the Arg59 residue central to the interaction. Computational modeling of mutational effect of this amino acid using Site Directed Mutator tool demonstrated increased stability of the F11R protein monomer. Additionally, protein interaction study using PDBsum tool demonstrated the weakening of the dimerization interaction by loss of a salt bridge between the interacting domains of the F11R protein monomers, indicating its plausible role in SCAD pathogenesis.