Abstract 12353: Genetic Basis of Left Ventricular Noncompaction
Purpose The purpose of this study was to investigate patients with Left ventricular noncompaction( LVNC) for mutations and investigate the role of SCN5A variants as phenotypic modifiers.
Methods We investigated 121 Japanese LVNC patients, including 47 familial cases and 74 sporadic cases, by direct DNA sequencing of genes previously associated with LVNC, including LIM domain binding protein 3 (LCB3/ZASP), α-dystrobrevin (DTNA), and tafazzin (TAZ/G4.5), genes encoding the sarcomeric proteins myosin binding protein 3 (MYBPC3), cardiac troponin T (TNNT2), β-myosin heavy chain (MYH7),α-tropomyosin (TPM1), and α-cardiac actin (ACTC), as well as the sodium channel α subunit gene (SCN5A).
Results DNA variants were identified in 27 patients including 21 cases from 14 families and 6 sporadic cases. The prevalence of the mutations in LDB3, TAZ, DTNA is only 7.5%. The sarcomeric gene mutations are most frequently found in our series; were found in 8 familial cases and 2 sporadic cases: In both sporadic cases, mutation were de novo. Interestingly, in 2 of the probands of familial cases, compound heterozygous variants were identified. These probands had the most severe phenotypes and appears to be a consequence of the compound mutations. In addition, the prevalence of SCN5A variants is significantly higher in LVNC patients with arrhythmias and/or heart failure than those without (p<0.001).
Conclusions The relatively small contribution of known mutations to the disease, compared to higher proportion of familial cases suggests that other elusive genes remain to be identified. The high incidence of variants in sarcomeric protein-encoding genes supports the concept that LVNC is part of a diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects and that there is a shared molecular etiology of different cardiomyopathic phenotypes. In addition, higher incidense of SCN5A variants in LVNC patients with arrhythmias and/or heart failure support the hypothesis that genes encoding ion channels are implicated in the pathophysiology of LVNC modifing the severity of disease.
- © 2011 by American Heart Association, Inc.