Massive Parallel Sequencing Of Idiopathic/ischemic Dilated Cardiomyopathy

Objects: With the rapid development of technology,the genetic basis of dilated cardiomyopathy(DCM)has made great progress.However,most of the research data of Chinese Han population are family research reports or small cohort studies involving a few genes.Considering the racial differences in genetic background,the genetic characteristics of Chinese DCM need further study.Methods: A total of 51 pathogenic genes of dilated cardiomyopathy were identified.We used the Ion Proton to establish a high-throughput re-sequencing method for these genes coding region.We have sequenced 230 Chinese Han DCM patients.The variation characteristics and genotype-phenotype correlation of Chinese Han patients were summarized.Results: The high-quality sequencing results were quickly obtained using this high-throughput sequencing,and we found protein-altering variants in 34 of 51DCM-pathogenic genes.Using a rigorous clinical variants classification,we found pathogenic or likely pathogenic mutations in 12.6% of idiopathic DCM patients and found one or more of the rare protein-altering variants in 49.5% of the patients;the TTN gene variants were still the most common and 59% of identified truncating variants were in TTN.We found that gene mutations were associated with early onset of disease.Patients with pathogenic/likely pathogenic mutations were 49.37 ± 12.23 years of age,significantly younger than those who did not carry the variants(55.94 ± 13.63 years)and who only had missense variants(55.87 ± 13.27 years)<0.05).No difference was found in cardiac structure and functional impairment between patients with or without variants.Conclusion: To our knowledge,this is the first study used a high-throughput sequencing platform to identify a large number of pathogenic genes in Chinese Han DCM patients,providing the most comprehensive genetic map of DCM in Chinese patients.We provided a convenient method for genetic testing of DCM patients and a reference for the interpretation of DCM gene variety in Han population.Objects: Although the concept of ischemic cardiomyopathy(ICM)has been widely used in clinical practice,its underlying mechanism is not fully understood.The degree of coronary artery disease/ ischemic injury and ventricular dilatation and damage function of the pathological condition is disproportionate.Therefore,there may be other mechanisms involved.This study intends to assess the impact of DCM pathogenic genes on the pathogenesis of ICM,and then explore whether ICM may share molecular genetic mechanism with DCM.Methods: In this study,based on the genetic analysis of idiopathic dilated cardiomyopathy in Chinese Han population,we used the second-generation sequencing method to detect cardiomyopathy gene variety in 180 ICM patients to explore whether patients with ICM mixed dilated cardiomyopathy,and the susceptibility of genetic variation in ICM patients.Results: In our study,10 patients with pathogenic/likely pathogenic mutations were found and the mutation burden was higher in patients with single lesion(4/26)than in patients with multiple lesions(6/154),showed a similar mutation load to DCM patients.In addition,we also detected 59 rare and protein-alter variants,the clinical significance of these variants are not clear,which may potentially increase the susceptibility of ICM patients.Conclusion: As far as we know,this is the first systematic study of genetic analysis in large number of in ICM patients based on coronary artery anatomic lesions.Only a small number of ICM patients identified pathogenic or likely pathogenic mutations,which suggest that the underlying mechanism of ICM still needs further study.