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Whole-exome sequencing reveals doubly novel heterozygous Myosin Binding Protein C and Titin mutations in a Chinese patient with severe dilated cardiomyopathy

Published online by Cambridge University Press:  15 August 2018

Liang-Liang Fan
Department of cell biology, the School of Life Sciences, Central South University, Changsha, China
Ya-Qin Chen
Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, China
Hao Huang
Department of cell biology, the School of Life Sciences, Central South University, Changsha, China
Jie-Yuan Jin
Department of cell biology, the School of Life Sciences, Central South University, Changsha, China
Jing-Jing Li
Department of cell biology, the School of Life Sciences, Central South University, Changsha, China
Zhi-Ping Tan*
Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China
Author for correspondence: Zhi-Ping Tan, PhD, Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, People’s Republic of China; E-mail:



Dilated Cardiomyopathy is a serious heart disorder that may induce sudden cardiac death and heart failure. Significant progress has been made in understanding the molecular basis of dilated cardiomyopathy. In previous studies, mutations in more than fifty genes have been identified in dilated cardiomyopathy patients. The purpose of this study was to detect the genetic lesion in a family from the central south of China affected by severe dilated cardiomyopathy.


Whole-exome sequencing combined with cardiomyopathy-related genes list were used to analyse the mutations of the proband. Co-segregation analysis was performed by Sanger sequencing.

Results and conclusions

Two novel heterozygous mutations – Myosin Binding Protein C: p.L1014RfsX6 and Titin: p.R9793X – were identified in the proband. The deletion mutation c.3041delT/p.L1014RfsX6 caused a premature stop codon at position 1020 in exon 28 of the Myosin Binding Protein C. The nonsense mutation, c.29377 C>T/ p. R9793X, of Titin was located in the highly evolutionarily conserved domain, resulting in truncation of the Titin protein as well. Co-segregation analysis further revealed that the Myosin Binding Protein C mutation came from his mother and the Titin mutation came from his father. Both mutations are reported in dilated cardiomyopathy patients for the first time. Our study not only provides a unique example of the genes and molecular mechanisms involved in dilated cardiomyopathy but also expands the spectrum of Myosin Binding Protein C and Titin mutations and contributes to the genetic diagnosis and counselling of dilated cardiomyopathy patients.

Original Article
© Cambridge University Press 2018 

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