Novel phenotype-genotype correlations of restrictive cardiomyopathy with myosin-binding protein c (mybpc3) gene mutations tested by next-generation sequencing

Background--mybpc3 dysfunctions have been proven to induce dilated cardiomyopathy,hypertrophic cardiomyopathy,and/or left ventricular noncompaction; however,the genotype-phenotype correlation between mybpc3 and restrictive cardiomyopathy (rcm) has not been established. the newly developed next-generation sequencing method is capable of broad genomic dna sequencing with high throughput and can help explore novel correlations between genetic variants and cardiomyopathies. methods and results--a proband from a multigenerational family with 3 live patients and 1 unrelated patient with clinical diagnoses of rcm underwent a next-generation sequencing workflow based on a custom ampliseq panel,including 64 candidate pathogenic genes for cardiomyopathies,on the ion personal genome machine high-throughput sequencing benchtop instrument. the selected panel contained a total of 64 genes that were reportedly associated with inherited cardiomyopathies. all patients fulfilled strict criteria for rcm with clinical characteristics,echocardiography,and/or cardiac magnetic resonance findings. the multigenerational family with 3 adult rcm patients carried an identical nonsense mybpc3 mutation,and the unrelated patient carried a missense mutation in the mybpc3 gene. all of these results were confirmed by the sanger sequencing method. conclusions--this study demonstrated that mybpc3 gene mutations,revealed by next-generation sequencing,were associated with familial and sporadic rcm patients. it is suggested that the next-generation sequencing platform with a selected panel provides a highly efficient approach for molecular diagnosis of hereditary and idiopathic rcm and helps build new genotype- phenotype correlations. © 2015 the authors.