Table 1.
Whole exome sequencing (WES)-identified genes affected in patients with diagnosed congenital heart disease (CHD).
| Heart Malformation | Identified Disease Genes | Reference |
|---|---|---|
| 362 parent-offspring trios with severe CHD (excluded isolated ventricular septal defects, atrial septal defects, patent ductus arteriosus and pulmonic stenosis) and 264 control trios | Genes involved in production, removal and reading of methylation of H3K4 (H3K4me): MML2, KDM6A, CHD7, WDR5, RNF20, UBE2B, SMAD2 | [44] |
| 2871 CHD cases including parent-offspring trios and 1789 controls | GDF1, MYH6, FLT4 CHD7, KMT2D, PTPN11, FLT4, NOTCH1, RBFOX2, SMAD6, GATA6, ELN, CCDC154, SLOCO1B3, GPBAR1, PTEN, RPL5, NSD1, SAMD11, C210RF2, NODAL, SMAD2, H1F00, FRYL, KDM5B, POGZ, SOS1, TBX18 | [41] |
| 715 CHD parent-offspring trios and 416 healthy individuals | Mosaic KMT2D mutations | [46] |
| TOF, combined with Cleft Lip and Palate | G586A and G196S variant of MTHFR | [47] |
| 8 TOF families | Novel causative mutations of PEX5, NACA, ATXN2, CELA1, PCDHB4, CTBP1 | [48] |
| 4 families with ASD, 2 families with PDA, 2 families with TOF and 1 family with dysplastic pulmonary valve | GATA4 G115W (ASD), TLL1 I263V (ASD kindred), MYH11 (ductus arteriosus). | [49] |
| 4-generation ASD family | Novel GATA4 A899C, and K300T variants | [50] |
| 79 subjects with BAV | GATA4/5, APC, JAG1, NOTCH1/2/3, PAX8, SOX9, TBX5, WNT4 | [37] |
| Left-sided lesions | 17 genes not previously associated with human cardiovascular malformation including ACVR1, JARID2, NR2F2, PLRG1, SMURF1. Gene established syndromic association with CHD such as KMT2D, NF1, TBX20, ZEB2. | [51] |
| 181 individuals from 41 families with LVOTO | NOTCH1, ARHGAP31, MAML1, SMARCA4, JARID2, JAG1. | [40] |
| 32 BAV patients | NOTCH1 G4297A and putative pathogenic ADMTS5 C935A. | [38] |
| Twins with heterotaxy | MMP21 | [52] |
| 1,365 trios with CHD, 68 probands from 32 multisibling families, and 458 singleton probands, 12,031 controls | CHD4, CDK13, PRKD1 | [53] |
| 59 CHD trios and 59 control trios, 100 affected singletons, 533 unaffected singletons |
Novel NR1D2 R175W mutation associated with AVSD, previously associated with CDH: ZFPM2, NSD1, NOTCH1, VCAN, and MYH6. | [54] |
| 3 family members with LVNC | Novel genetic variant of MYH7 gene | [55] |
ASD: atrial septal defects; AVSD: atrioventricular septal defect; BAV: bicuspid aortic valve; LVNC: left ventricular non-compaction; LVOTO: left-ventricular outflow tract obstructions; TOF: tetralogy of Fallot.