ena-STUDY-PRIF UK-21-11-2017-11:51:14:648-1363
Diagnostic yield of a next-generation sequencing gene panel in Slovak cardiomyopathy patients
Next-generation sequencing of known cardiomyopathy gene panels is generally considered the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. For the first time we use a panel of 46 known cardiomyopathy-associated genes to detect candidate pathogenic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). We identified candidate pathogenic variants in 11 of 16 patients (69%) in 9 known genes. Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Six variants TPM1 (c.572G>A), MYBPC3 (c.842G>A), MYH6 (c.253G>A), PKP2 (c.1487T>A), DSP (c.484C>G), MYH7 (c.1988G>A) have already been detected in other cardiomyopathy cohorts. Ten variants MYBPC3 (c.3407_3409delACT, c.373_374delGC), MYH7 (c.746G>A, c.1025C>T), PKP2 (c.2003delA), TTN (c.101874_101881delAGAATTTG, c.51655C>T, c.84841G>T), ACTC1 (c.329C>T) and ANKRD1 (c.683G>T) have been detected for the first time and might represent Slovak-specific genetic cause. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia.
Next-generation sequencing of known cardiomyopathy gene panels is generally considered the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. For the first time we use a panel of 46 known cardiomyopathy-associated genes to detect candidate pathogenic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). We identified candidate pathogenic variants in 11 of 16 patients (69%) in 9 known genes. Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Six variants TPM1 (c.572G>A), MYBPC3 (c.842G>A), MYH6 (c.253G>A), PKP2 (c.1487T>A), DSP (c.484C>G), MYH7 (c.1988G>A) have already been detected in other cardiomyopathy cohorts. Ten variants MYBPC3 (c.3407_3409delACT, c.373_374delGC), MYH7 (c.746G>A, c.1025C>T), PKP2 (c.2003delA), TTN (c.101874_101881delAGAATTTG, c.51655C>T, c.84841G>T), ACTC1 (c.329C>T) and ANKRD1 (c.683G>T) have been detected for the first time and might represent Slovak-specific genetic cause. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia.