Discovering Genotype Variants in an Infant with VACTERL through Clinical Exome Sequencing: A Support for Personalized Risk Assessment and Disease Prevention.

Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by "Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb" (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G>C on and c.-8C>G on were previously associated with myocardial infarction. The variants c.1936A>G on and c.575A>G on are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G>A on and c.214C>A on . In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on and c.91T>A on proto-oncogenes as well as c.827A>C in the tumor suppressor . A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (, , , , ) and eight proto-oncogenes (, , , , , , , ) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.