Table 4 Pathogenic or likely pathogenic sequence variants identified in the 62 fetuses with CHDs
Case | Cardiac defects | Extracardiac malformations | Gene | Sequence variant | Genotype | Origin | Classification | Disorders (OMIM number; Mode of inheritance) | Reported variant | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
1 | HLHS | Hydronephrosis, renal agenesis | KMT2D | NM_003482.4:c.5485dup(p.Ile1829Asnfs*4) | Het | Dn | P | Kabuki syndrome 1 (147,920; AD) | No | TOP |
2 | HLHS | – | WAC | NM_016628.5:c.1394delT(Ile465Thrfs*4) | Het | Dn | P | Desanto-Shinawi syndrome (616,708; AD) | No | TOP |
3 | d-TGA, DORV, VSD, ASD | – | CHD7 | NM_017780.4: c.3018delT (p.Leu1007Serfs*6) | Het | Dn | P | CHARGE syndrome (214,800; AD); Hypogonadotropic hypogonadism 5 with or without anosmia (612,370; AD) | No | TOP |
4 | VSD | – | RAF1 | NM_002880.4: c.1082G > C (p.Gly361Ala) | Het | Dn | P | Noonan syndrome 5 (611,553; AD); LEOPARD syndrome 2 (611,554; Un); Cardiomyopathy, dilated, 1NN (615,916; AD) | Yes | TOP |
5 | VSD + IAA | Hydrocephalus, hypospadias | EP300 | NM_001429.4:c.3671 + 1G > A | Het | Dn | LP | Menke-Hennekam syndrome 2 (618,333; AD), Rubinstein-Taybi syndrome 2 (613,684; AD) | Yes | TOP |
6 | AVSD | – | GDF1 | NM_001492.6:c.996delC(p.Asp333Thrfs*52) | Het | Dn | LP | Congenital heart defects, multiple types, 6 (613,854; AD) | No | TOP |
7 | DORV, VSD | FGR, facial flatness, suspected craniosynostosis | PQBP1 | NM_001032382.2: c.459_462del (p.Arg153Serfs*41) | Hemi | Mat | P | Renpenning syndrome (309,500; XLR) | Yes | TOP |
8 | VSD, COA | - | LZTR1 | NM_006767.4: c.851G > A (p.Arg284His) | Het | Pat | LP | Noonan syndrome 10 (616,564; AD); Noonan syndrome 2 (605,275; AR) | Yes | TOP |
|  |  |  | SOS2 | NM_006939.4:c.708A > T(p.Lys236Asn) | Het | Mat | VUS | Noonan syndrome 9 (616,559; AD) | No |  |