Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity.
Pascale RichardFlavie AderMaguelonne RouxErwan DonalJean-Christophe EicherNadia AoutilOlivier HuttinChristine Selton-SutyDamien CoisneGuillaume JondeauThibaud DamyNicolas MansencalAnne-Claire CasaltaNicolas MichelJulie HaentjensLaurence FaivreCecile LavouteKarine NguyenDavid-Alexandre TregouëtGilbert HabibPhilippe CharronPublished in: Clinical genetics (2018)
Left ventricular non-compaction (LVNC) is a cardiomyopathy that may be of genetic origin; however, few data are available about the yield of mutation, the spectrum of genes and allelic variations. The aim of this study was to better characterize the genetic spectrum of isolated LVNC in a prospective cohort of 95 unrelated adult patients through the molecular investigation of 107 genes involved in cardiomyopathies and arrhythmias. Fifty-two pathogenic or probably pathogenic variants were identified in 40 patients (42%) including 31 patients (32.5%) with single variant and 9 patients with complex genotypes (9.5%). Mutated patients tended to have younger age at diagnosis than patients with no identified mutation. The most prevalent genes were TTN, then HCN4, MYH7, and RYR2. The distribution includes 13 genes previously reported in LVNC and 10 additional candidate genes. Our results show that LVNC is basically a genetic disease and support genetic counseling and cardiac screening in relatives. There is a large genetic heterogeneity, with predominant TTN null mutations and frequent complex genotypes. The gene spectrum is close to the one observed in dilated cardiomyopathy but with specific genes such as HCN4. We also identified new candidate genes that could be involved in this sub-phenotype of cardiomyopathy.
Keyphrases
- genome wide
- copy number
- left ventricular
- end stage renal disease
- dna methylation
- heart failure
- ejection fraction
- newly diagnosed
- chronic kidney disease
- genome wide identification
- single cell
- aortic stenosis
- peritoneal dialysis
- bioinformatics analysis
- prognostic factors
- acute myocardial infarction
- gene expression
- genome wide analysis
- smoking cessation
- deep learning
- congenital heart disease
- human immunodeficiency virus