title: Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing.
abstract: Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death. Mutations in the MYBPC3 gene represent the cause of HCM in ~35% of patients with HCM. However, genetic testing in clinic setting has been limited due to the cost and relatively time-consuming by Sanger sequencing. Here, we developed a HCM Molecular Diagnostic Kit enabling ultra-low-cost targeted gene resequencing in a large cohort and investigated the mutation spectrum of MYBPC3. In a cohort of 114 patients with HCM, a total of 20 different mutations (8 novel and 12 known mutations) of MYBPC3 were identified from 25 patients (21.9%). We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients. Phenotype-genotype analyses showed that the patients with double mutations (n = 2) or premature termination codon mutations (n = 12) showed more severe manifestations, compared with patients with missense mutations (n = 11). Particularly, we identified a recurrent truncation mutation (p.Y842X) in four unrelated cases (4/25, 16%), who showed severe phenotypes, and suggest that the p.Y842X is a frequent mutation in Chinese HCM patients with severe phenotypes.
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Xuxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Tengyong
authors.initials: T
authors.lastname: Jiang
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Piao
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zheng
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: 1] Beijing Anzhen Hospital, Capital Medical University, Beijing, China [2] Beijing Collaborative Innovation Center for Cardiovascular Disorders [3] The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D023061:Gene Order; D056726:Genetic Association Studies; D005838:Genotype; D006325:Heart Atria / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C