Table 1.
CRISPR-Cas9 in congenital heart diseases (CHDs)
| CHD | Causative gene (s) | Mutations | Cardiac anomalies | Model system | Cas9 | Ref. |
|---|---|---|---|---|---|---|
| DiGeorge syndrome | DGCR2 | DGCR2 destroy | IAA | Mouse TT2 ES cell | NFL-hCas9; sgRNA exon4 | 106 |
| PTA | ||||||
| TBX1 | Knockout | TOF | E14-Tg2a mESCs | Alt-R | 105 | |
| VSD | SpCas9 | |||||
| Barth syndrome | TAZ | 328T>C | DCM | Human IPSC line | Cas9 | 100 |
| Wolff-Parkinson-White | PRKAG2 | H530R | VT | Mouse | Cas9 | 79 |
| Duchenne muscular dystrophy | Dystrophin | Nonsense mutation (exon 23) | DCM | Mouse, zygote | Cas9 mRNA | 82 |
| Mouse | aav9-SaCas9 | 83 | ||||
| Holt-Oram syndrome | TBX5 | zTbx5b knockout | ASD, AVSD, progressive AV conduction disease | Zebrafish | Cas9 mRNA | 91 |
| sgRNA | ||||||
| 243-1G>C | 134 | |||||
| 148-1G>C | 135 | |||||
| S196ter, DGlu243Fter, R237W | 87 | |||||
| Heterotaxy syndrome | ZIC3 | 890G > T (C297F) | DILV, DORV, d-TGA, AVSD, SA, TA, TGA, PA, VSD, PDA, LSVC | 93 | ||
| 680dup | Zebrafish mutation | 96 | ||||
| 842_843del | ||||||
| 869del | ||||||
| 1063G>T | ||||||
| 1111A>C | ||||||
| 1060+1G>A | ||||||
| DNAH10 | 12q24.31 3-duplicate | Zebrafish knockout | zCas9 mRNA | 97 | ||
| RNF115 | 1q21.1 1-deletion | Zebrafish knockout | zCas9 mRNA | 97 | ||
| CFC1 | R78W, R112C, R189C, G174del1 | mouse, zebrafish | 136 | |||
| Noonan syndrome | PTPN11 | 922A > G, c.923A > G (exon 8) | PVS | 137 | ||
| HCM | ||||||
| exon 2,3,4,7,8, 13 | 138 | |||||
| T59A | 139 | |||||
| LZTR1 | Intronic | iPSC | Cas9 | 103 | ||
| KRAS | 458A > T | 140 | ||||
| RAF1 | S259T | 139 | ||||
| SOS1 | K170E | delayed psychomotor development | 139 | |||
| Marfan syndrome | FBN1 | 4282 delC 7_8insTC 2192 delC | AoD, AD, MVP | 141 | ||
| T7498C | Human embryo | BE3 | 125 | |||
| FBLN4 | 1189G>A (exon 11) | 142 | ||||
| TGFBR2 | W521R R528H R537P | Zebrafish | 143 | |||
| TGFBR1 | 973+1G>A 806-2A>C (exon5) | 144 | ||||
| Nonsyndromic | GATA4 | G296S | ASD, VSD | iPSC | spCas9 (H840A) | 109 |
| MyHC6 | R443P | HLHS | iPSC | Cas9 | 123 | |
| NKX2.5 | A119S | LVNC | iPSC | Cas9 | 111 | |
| MYH7 | L387F | LVNC | iPSC | Cas9 | 111 | |
| MKL2 | Q670H | LVNC | iPSC | Cas9 | 111 |
CRISPR-Cas9, clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9; AD, aortic root dissection; AoD, aortic root dilation; ASD, atrial septal defect; AVSD, atrioventricular septal defect; BE3, base editing 3; BI, bronchial inversus; BRB, bilateral right bronchi (short); BSVC, bilateral superior vena cava; CAVC, complete atrioventricular canal; CCD, cardiac conduction disease; D, dextrocardia; d-TGA, D-transposition of the great vessels; DCM, dilated cardiomyopathy; DILV, double inlet left ventricle; DOLV, double-outlet left ventricle; DORV, double-outlet right ventricle; dup duplication; del deletion; HCM, hypertrophic cardiomyopathy; HLHS, hypoplastic left heart syndrome; iPSCs, induced pluripotent stem cells; IQR, interquartile range; IRAA, isomerism of right atrial appendages; LAA, left aortic arch; LCS, liver centrally situated; LSL, left-sided liver; LSS, left-sided stomach; LSVC, left superior vena cava, LVNC, left ventricular noncompaction cardiomyopathy; MVP, mitral valve prolapse; PA pulmonary atresia; PAVC, partial atrioventricular canal; PDA, patent ductus arteriosus; PLSVC, persistent left superior vena cava; PS, pulmonary stenosis; PTA, persistent truncus arteriosus; PVS, pulmonary valve stenosis; RAA, right aortic arch; RSS, right-sided stomach; SA, single atrium; SIV, superior-inferior ventricle; SV, single ventricle; TA, tricuspid atresia; TGA, transposition of the great arteries; TGA/MGA, translocation of great arteries/malposition of great arteries; TOF, tetralogy of Fallot; TPAVD, total anomalous pulmonary venous drainage; VSD, ventricle septum defect; IAA, interrupted aortic arch; VT, ventricular tachyarrhythmia.