Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association.
Eur J Pediatr Surg
; 32(1): 61-66, 2022 Feb.
Article
en En
| MEDLINE
| ID: mdl-34823266
ABSTRACT
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 ANDMETHODS:
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades Vasculares
/
Cardiopatías Congénitas
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Eur J Pediatr Surg
Asunto de la revista:
PEDIATRIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania