Abstract 17900: Sarcomere Gene Mutations in Left Ventricular Noncompaction
Introduction: Left ventricular noncompaction (LVNC) is a primary cardiomyopathy with heterogeneous genetic origins, however, the genetic basis of disease in a large proportion of patients with LVNC is still unresolved. We evaluated the potential clinical impact of genetic analysis of sarcomere genes in patients with LVNC.
Methods: We investigated 93 Japanese LVNC patients, including 23 familial cases, for mutations of genes encoded sarcomeric proteins including myosin binding protein C (MYBPC3), β-myosin heavy chain (MYH7), α-tropomyosin (TPM1), cardiac troponin T (TNNT2), α-cardiac actin (ACTC) and cardiac troponin I (TNNI3). Of these 49 were infants and 44 were juvenile cases.
Results: We identified 28 sarcomeric gene mutations in 32 patients (34%) including 17 infants and 15 juvenile cases . These mutations were distributed among 5 genes, 12 in MYH7 and 9 in MYBPC3, 3 in TPM1, 2 in TNNT2, and 2 in ACTC1. Nineteen (68%) of the mutations were novel, affected conserved amino acid residues and were predicted to alter the structure of the proteins by in silico analysis. MYH7 and MYBPC3were the most prevalent disease genes and accounted for 81% of cases with mutation. Of note, 2 infants and 2 juvenile cases were compound or double heterozygous for 2 different mutations, and showed the most severe phenotype. Although most of the infants had clinical signs or symptoms of heart failure at initial presentation (88%), the majorities of juvenile cases were asymptomatic and identified only when screened for cardiac abnormalities, such as ECG screening (57%). Comparing sarcomere mutation-positive and mutation-negative LVNC probands showed no significant differences with respect to clinical characteristics at baseline and mortality during follow up both in infants and juvenile cases.
Conclusions: Mutations in sarcomere genes account for a significant proportion of patients with LVNC both in infants and juvenile cases. High incidence of novel mutations supports the concept that LVNC is part of a diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects.
Author Disclosures: A. Takasaki: None. Y. Hata: None. K. Hirono: None. N. Hideyuki: None. K. Ibuki: None. S. Ozawa: None. N. Yoshimura: None. N. Nishida: None. F. Ichida: None.
- © 2014 by American Heart Association, Inc.