title: Novel Phenotype-Genotype Correlations of Restrictive Cardiomyopathy With Myosin-Binding Protein C (MYBPC3) Gene Mutations Tested by Next-Generation Sequencing.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (W.W., W.C., Y.T.L., Y.C.H., S.Y.Z.).
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (C.X.L., F.L., X.Z.).
authors.forename: Chao-Xia
authors.initials: CX
authors.lastname: Lu
authors.affiliation: Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (Y.N.W., J.C.).
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Wang
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (C.X.L., F.L., X.Z.).
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (W.W., W.C., Y.T.L., Y.C.H., S.Y.Z.).
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (W.W., W.C., Y.T.L., Y.C.H., S.Y.Z.).
authors.forename: Yong-Tai
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (W.W., W.C., Y.T.L., Y.C.H., S.Y.Z.).
authors.forename: Ye-Chen
authors.initials: YC
authors.lastname: Han
authors.affiliation: Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (Y.N.W., J.C.).
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (W.W., W.C., Y.T.L., Y.C.H., S.Y.Z.).
authors.forename: Shu-Yang
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China (C.X.L., F.L., X.Z.).
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D002313:Cardiomyopathy, Restrictive / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods*; D018618:Echocardiography, Doppler, Color; D017548:Echocardiography, Transesophageal; D004562:Electrocardiography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000235:genetics; D057188:Workflow; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D000099163:Myosin Binding Protein C
keywords: diastolic dysfunction; genotype–phenotype; restrictive cardiomyopathy