Published online Apr 16, 2023. doi: 10.12998/wjcc.v11.i11.2412
Peer-review started: November 12, 2022
First decision: February 14, 2023
Revised: February 22, 2023
Accepted: March 15, 2023
Article in press: March 15, 2023
Published online: April 16, 2023
Processing time: 145 Days and 3 Hours
Dilated cardiomyopathy (DCM) is a type of genetically heterogeneous cardiomyopathy; it is the primary cause of heart transplantation and the third most common cause of heart failure, malignant arrhythmia, and sudden death. Although DCM has obvious genetic heterogeneity, with nearly 50% of DCM cases caused by genetic factors that are dominant in pathogenesis, research on the pathogenic genes associated with DCM is lacking.
With the development of next-generation sequencing technology, it has recently been found that DCM is related to variations in a number of genes encoding sarcomeric, cytoskeletal, nuclear membrane, and desmosomal proteins. However, only ~40% of familial DCM patients harbor known hereditary changes in pathogenic genes, while the etiology of the remaining 60% of familial DCM patients remains unclear. Therefore, the identification of pathogenic genes in DCM through pedigree analysis has become critical in the field of cardiovascular disease.
Our research team identified a typical DCM pedigree clinically. This study aimed to identify pathogenic genes in DCM through pedigree analysis.
Our research team sequenced the whole exomes of seven samples in the pedigree using high-throughput sequencing technology, namely next-generation sequencing, and verified the potential candidate gene mutations in nineteen samples of the pedigree using Sanger sequencing. Then, we identified the sample sequence mutations using bioinformatics methods, and identified the family pathogenic gene mutations according to the family sample clinical information and gene variation annotation information.
A novel and potentially pathogenic gene mutation-ANK2p.F3067L-was discovered. The codon changes to c.T9199C and the amino acid changes to p.F3067L (phenylalanine mutates to leucine). It is a non-synonymous mutation (i.e., missense mutation).
The mutation-ANK2p.F3067L was completely consistent with the clinical information for this DCM pedigree. It is considered a novel and potentially pathogenic gene mutation in DCM.
Our study adds new members to DCM pathogenic genes, and makes a significant contribution to the literature. It would be useful for clinical implications of these results in medicine, especially general medicine.