The Cumulative Effects of the MYH7-V878A and CACNA1C-A1594V Mutations in a Chinese Family with Hypertrophic Cardiomyopathy.

Abstract

AIMS:

We investigated the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations in a Chinese family with hypertrophic cardiomyopathy.

METHODS:

Clinical, electrocardiographic (ECG), echocardiographic, and cardiac magnetic resonance (CMR) examinations of members of a Chinese family were followed by exon and boarding intron analyses of 96 genes in the proband using second-generation sequencing. We confirmed the mutations by bidirectional Sanger sequencing in the members and in 300 healthy controls.

RESULTS:

We detected MYH7-V878A and CACNA1C-A1594V mutations in this family. The members with both mutations showed inverted T-waves and ST-segment depression in ECG recordings, severe left ventricular (LV) hypertrophy in echocardiography, and myocardial fibrosis in CMR; subject II-11 did not show late gadolinium enhancement. Among those with only the MYH7-V878A mutation, subject III-7 showed abnormal ECG recordings, asymmetric septal hypertrophy, and myocardial fibrosis, and subjects II-13 and III-15 showed some abnormal repolarization, borderline LV wall thickness, and normal CMR findings. Those with only the CACNA1C-A1594V mutation showed nearly normal readings in all examinations. The members with both mutations displayed more severe LV hypertrophy and elevated LV filling pressure than those with 1 or no mutation (p < 0.05).

CONCLUSION:

Our results suggest that the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations may have a cumulative effect.

• Authors: Bo Wang, Rui-Qi Guo, Jing Wang, Fan Yang, Lei Zuo, Ying Liu, Hong Shao, Yan Ju, Chao Sun, Lei Xu, Yan-Min Zhang, Li-Feng Wang, Li-Wen Liu
• Journal: Cardiology (Cardiology) 2017 Vol. 138 Issue 4 Pg. 228-237 ISSN: 1421-9751 [Electronic] Switzerland
• PMID: 28866666 (Publication Type: Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• CACNA1C protein, human
• Calcium Channels, L-Type
• MYH7 protein, human
• Cardiac Myosins
• Myosin Heavy Chains

Topics

• Adolescent
• Adult
• Asian People (genetics)
• Calcium Channels, L-Type (genetics)
• Cardiac Myosins (genetics)
• Cardiomyopathy, Hypertrophic (genetics, physiopathology)
• Case-Control Studies
• Child
• Echocardiography
• Electrocardiography
• Exons
• Female
• Heart Ventricles (physiopathology)
• Humans
• Hypertrophy, Left Ventricular (diagnostic imaging)
• Male
• Middle Aged
• Mutation
• Myosin Heavy Chains (genetics)
• Young Adult