Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association
dx.doi.org shows its articles on its own site.
Read the article on dx.doi.org ↗Article · Nov 2021 · 1 min read
In brief
In brief
Whole exome sequencing of 21 VACTERL patients identified damaging genetic variants in cardiovascular development genes in every case, supporting a genetic basis for vascular disorders triggering this malformation complex. The study found 39 significant variants across 33 genes, with sibling cases sharing identical variants, suggesting hereditary vascular pathology may underlie VACTERL phenotypes.
Written by the GCMD Library team from the article.
Introduction The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association.
Materials and Methods We performed a functional analysis on whole exome sequencing data of 21 patients with VACTERL or VACTERL-like phenotype using the online analysis tool “Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8.†The study was approved by the institutional ethics committee (approval no. 026–13). Written informed consent was obtained from all patients or their parents.
Results We identified a total of 86 genetic variants (in 75 genes) classified as damaging (including probably damaging missense, nonsense, and frameshift variants), which are associated to cardiovascular development. Each investigated patient showed at least one damaging variant in genes associated to cardiovascular development. These variants were further reduced by significance in cardiovascular development to 39 genetic variants (in 33 genes). Of note, a pair of siblings, both presenting with cardiac and renal defects, had the same damaging variant in two different genes.
Conclusion Our results indicate a genetic background for congenital vascular disorders in patients with VACTERL association. In line with the literature, our data suggest that genetic mutation led to vascular diseases, which in turn may cause malformations similar to the VACTERL association.