Table 1.
Phenotype data and most relevant alterations. List of the studied samples with information on gender, gestational age and phenotype (specifying the heart malformation) of the 16 fetuses with syndromic (DS) and isolated congenital heart defect (iCHD). The most relevant regions showing aberrant methylation per sample and the status and location of the aberrant methylation with respect to the closest gene are displayed in the 2 last columns. TOF: tetralogy of Fallot; RHH: right heart hypoplasia; HAA: hypoplasia of the ascending aorta; LHH: left heart hypoplasia; VSD: ventricular septal defect; D-TGA: dextro-transposition of the great arteries; L-TGA: levo-transposition of the great arteries; AVSD: atrioventricular septal defect; MVA: mitral valve atresia; ADA: aneurismatic dilatation of the atrium; AVA: aortic valve atresia; TAV: tricuspid aortic valve; DORV: double outlet right ventricle, CoA: coarctation of the preductal aorta; TVS: tricuspid valve stenosis; TA: truncus arteriosus; ADA: absent ductus arteriosus; PFO: patent foramen ovale
| Sample | Gender | Weeks of gestation | Phenotype | Regions with altered methylation profile | Genes included in the regions (region and status) |
|---|---|---|---|---|---|
| Control_1 | Female | 20 | Normal development | — | — |
| Control_2 | Female | 15 | Normal development | — | — |
| Control_3 | Female | 15 | Normal development | — | — |
| Control_4 | Male | 20 | Normal development | — | — |
| DS_1 | Female | 19 | DS | — | — |
| DS_2 | Female | 22 | DS | — | — |
| DS_3 | Female | 22 | DS | — | — |
| DS_4 | Female | 22 | DS | — | — |
| DS_5 | Female | 18 | DS | — | — |
| DS_6 | Male | 20 | DS | — | — |
| DS-CHD_1 | Female | 22 | DS and VSD | 5 | HTR3C (hypo), MT1X (hyper), IDH3G (hyper), GZMH (hypo), TCL1B (hyper), TCL6 (hyper), TML1 (hyper) |
| DS-CHD_2 | Female | 22 | DS and VSD | 4 | CD80 (hypo), IGDCC3 (hypo), IGDCC4 (hypo), FFAR3 (hypo), CBR1 (hyper), SETD4 (hyper) |
| DS-CHD_3 | Female | 18 | DS, AVSD and CoA | 2 | DOK7 (hyper), NOS3 (hypo) |
| DS-CHD_4 | Female | 19 | DS and TOF | 1 | SLC2A1 (hyper) |
| DS-CHD_5 | Male | 22 | DS and VSD | 3 | ZFP2 (hyper), RAET1L (hyper), KIAA0101 (hyper), |
| DS-CHD_6 | Female | 18 | DS, LHH and HAA | 5 | BIN1 (hyper), UBE2H (hyper), CHP (hyper), NXN (hyper), TCL1B (hyper), TCL6 (hyper), TML1 (hyper) |
| iCHD_1 | Male | 22 | DORV, VSD and HAA | 3 | MSX1 (hyper), CST8 (hypo), GZMH (hypo) |
| iCHD_2 | Female | 22 | TOF | 8 | RPL10A (hyper), PIM1 (hyper), C7orf25 (hyper), NPR2 (hyper), KRT71 (hypo), HRK (hyper), LZTR1 (hyper), SERHL (hyper), |
| iCHD_3 | Female | 21 | LHH, MVA, AVA and HAA | 1 | TNR (hypo) |
| iCHD_4 | Female | 22 | DORV, PFO, VSD and CoA | 2 | IGFBP3 (hyper), MTHFS (hyper) |
| iCHD_5 | Female | 22 | TVS, RHH, VSD, MVA and AA | 3 | CHST11 (hypo), MYO1E (hyper), TCL1B (hyper), TCL6 (hyper), TML1 (hyper) |
| iCHD_6 | Female | 22 | TA-type II, ADA, TAV, VSD | 0 | — |