Toward Precision Medicine in Aortopathies: Genetic Insights from a Brazilian Cohort Through Targeted Next-Generation Sequencing

Abstract

ABSTRACTThoracic aortic diseases (or aortopathies) result from complex interactions between genetic and hemodynamic factors. Often clinically silent, these diseases can lead to lethal complications like aortic dissection or rupture. This study focused on a Brazilian cohort of 79 individuals with thoracic aortic diseases, exploring genetic factors through targeted next-generation sequencing (tNGS) of 15 priority genes. The majority of individuals had non-syndromic aortopathy, with eight diagnosed with Marfan syndrome (MFS). Pathogenic or likely pathogenic variants (PV/LPV) were found in five genes, including FBN1, ACTA2, TGFBR2, MYLK, and SMAD3. Notably, novel variants in FBN1 were identified, contributing to Marfan-like phenotypes. The diagnostic yield for isolated aortopathies was 7.1%, rising to 55.5% for syndromic cases. Variants of uncertain significance (VUS) were identified, emphasizing the need for further research and familial investigations to refine variant classifications. This study provides valuable insights into the genetic landscape of aortopathies in Brazil, aiding early diagnosis and personalized management.