Familial dilated cardiomyopathy associated with congenital defects in the setting of a novel VCL mutation (Lys815Arg) in conjunction with a known MYPBC3 variant

  • Quinn S. Wells Center for Inherited Heart Disease, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
  • Natalie L. Ausborn Center for Inherited Heart Disease, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
  • Birgit H. Funke Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine, Cambridge, MA, United States.
  • Jean P. Pfotenhauer Center for Inherited Heart Disease, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
  • Joseph L. Fredi Center for Inherited Heart Disease, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
  • Samantha Baxter Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine, Cambridge, MA, United States.
  • Thomas G. DiSalvo Center for Inherited Heart Disease, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.
  • Charles C. Hong | charles.c.hong@Vanderbilt.Edu Center for Inherited Heart Disease, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine; Research Medicine, Veterans Affairs TVHS, Nashville, TN, United States.

Abstract

Idiopathic dilated cardiomyopathy (DCM) is a primary myocardial disorder characterized by ventricular chamber enlargement and systolic dysfunction. Twenty to fifty percent of idiopathic DCM cases are thought to have a genetic cause. Of more than 30 genes known to be associated with DCM, rare variants in the VCL and MYBPC3 genes have been reported in several cases of DCM. In this report, we describe a family with DCM and congenital abnormalities who carry a novel missense mutation in the VCL gene. More severely affected family members also possess a second missense variant in MYBPC3, raising the possibility that this variant may be a disease modifier. Intere - stingly, many of the affected individuals also have congenital defects, including two with bicuspid aortic valve with aortic regurgitation. We discuss the implications of the family history and genetic information on management of at-risk individuals with aortic regurgitation.

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References

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Published
2011-08-22
Info
Issue
Section
Brief Reports
Supporting Agencies
National Institutes of Health, Edwards Lifesciences Fund
Keywords:
dilated cardiomyopathy, vinculin, myosin binding protein C, VCL, MYBPC.
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How to Cite
Wells, Q., Ausborn, N., Funke, B., Pfotenhauer, J., Fredi, J., Baxter, S., DiSalvo, T., & Hong, C. (2011). Familial dilated cardiomyopathy associated with congenital defects in the setting of a novel VCL mutation (Lys815Arg) in conjunction with a known MYPBC3 variant. Cardiogenetics, 1(1), e10. https://doi.org/10.4081/cardiogenetics.2011.e10