Diagnostic and prognostic relevance of using large gene panels in the genetic testing of patients with dilated cardiomyopathy

Genetic testing is often performed in patients with a dilated cardiomyopathy (DCM) who also have a family history of the condition. These tests look at a variety of genes known to be associated with DCM, searching for mutations that might be causing the disease. The set of genes being tested is called a “gene panel.” It has previously been suggested that testing more genes in DCM patients will lead to an increase in finding a gene mutation. This study looked at whether using larger gene panels for testing can help to increase the number of mutations and predict how DCM will progress.

This research included 225 DCM patients who had not been found to have a gene mutation using a smaller panel of 48 genes. These patients were then tested with a much larger, 299-gene panel, known as the HEART-panel, to see if additional mutations could be detected.

These are the main discoveries:

  1. Finding Disease-Causing Genes: Even with the larger HEART-panel, only a small number of new gene mutation were found in these patients. This suggests that simply testing more genes doesn’t always help find the cause of DCM.
  2. Understanding Risk: using larger panels increased the finding of changes in DNA whose significance for the disease is unclear, known as ‘variants of uncertain significance’ or VUS.

The main takeaway is that simply testing a larger number of genes doesn’t necessarily improve the identification of genetic mutations in DCM patients. More ‘variants of uncertain significance’ were identified with big gene panels that could even lead to more uncertainty. The researchers suggest to focus only on key genes associated with DCM when performing genetic testing, using small targeted panels​.

 

Link to full article

Stroeks SLVM, Hellebrekers D, Claes GRF, Krapels IPC, Henkens MHTM, Sikking M, Vanhoutte EK, Helderman-van den Enden A, Brunner HG, van den Wijngaard A, Verdonschot JAJ. Diagnostic and prognostic relevance of using large gene panels in the genetic testing of patients with dilated cardiomyopathy.

Eur J Hum Genet. 2023 Jul;31(7):776-783. doi: 10.1038/s41431-023-01384-y. Epub 2023 May 17. PMID: 37198425; PMCID: PMC10325988.

Prepared by Drs Stroeks and Verdonschot and Ruth Biller

 

de Frutos et al. J Am Coll Cardiol. 2022 80, 1447–1461.