Table 2.
Gene | Species | Mutation/effect on gene expression | CHDs associated with mutation/developmental process | References |
---|---|---|---|---|
MYH3 | Chick | Knockdown | Ab atrial and trabeculae development; enlarged heart; abnormal AP and calcium and potassium transients | [42] |
MYH6 | Human | I820N | ASD | [2] |
A230P | TA | [58] | ||
H252Q | TGA, PFO | |||
E501Stop | TA | |||
V700M | PFO | |||
A1366D | AS, SDK, SAR, PFO | |||
A1443D | ASD | |||
R1865Q | ASD, DIVC, VSD | |||
IVS37-2A > G | ASD, PTA | [59] | ||
R17H | ASD, AVSD, SVC/CS | |||
C539R | ASD | |||
K543R | ASD | |||
A1004S | ASD | |||
Chick | Knockdown | Ab atrial septal development | [2, 61] | |
Ab trabeculae development; looping defects, EH | [61] | |||
Ab calcium transients in atrium | [42] | |||
Mouse | Homozygous | Death E11–12.5, heart phenotype ND | [60] | |
Heterozygote | Viable, fertile, Ab cardiac function, fibrotic lesions, Ab sarcomeres | [60] | ||
Zebrafish | Weak atrium homozygous | Absent contraction, Ab myofibrillogenesis in atrium | [53] | |
Xenopus | Muzak homozygous | Absent myofibrils and cardiac contraction, EH | [62] | |
MYH7 | Human | R281T | ASD, EA | [65] |
Y283D | ASD, VSD, pulAH | [66] | ||
Y350N | EA | |||
L390P | EA, PFO | |||
K1459N | EA | |||
N1918K | Coa/BAV | |||
E1573K | VSD | |||
1220delE | EA | |||
Chick | Knockdown | Ab calcium transients in atrium and ventricle | [42] | |
EH | UnD | |||
Zebrafish | Half-hearted | Enlarged ventricle, fewer myofibrils, increased cardiomyocytes | [70] | |
Medaka fish | Hozuki mutant | Enlarged ventricle, increased cardiomyocytes | [71] | |
MYH10 | Mouse | Homozygous | VSD, DORV, hypertrophic cardiac myocytes | [78] |
MYH11 | Human | IVS32 + 1G to T | TAAD | [82] |
R1758Q | ||||
R1241_L1264del | ||||
L1264P | TAAD, PDA | [83] | ||
R1275L | ||||
R712Q | ||||
R669C | PDA | [84] | ||
E1290Q | ||||
Mouse | Homozygous | PDA | [85] | |
MYL2 | Mouse | Homozygous null | Death E12.5, EH, wall thinning, Ab sarcomeres | [97] |
Chick | Knockdown | Ab cardiac looping, Ab sarcomeres | [91] | |
MYL4 | Zebrafish | Knockdown | Ab sarcomeres with increased length, decreased contractility | [110] |
MYL7 | Mouse | Homozygous null | Death E10.5–11.5, EH tube, Ab looping, Ab trabeculae, left ventricular dilation, Ab myofibril assembly | [121] |
Zebrafish | Knockdown | Ab sarcomeres with decreased length and contractility, EH | [110] | |
Tell tale homozygous | Ab contraction, Ab sarcomeres | [120] |
Only mutations and phenotypes related to cardiac development are described; mutations and phenotypes related to cardiac function e.g., cardiomyopathy, are not listed
Ab abnormal, AP action potential, AS aortic stenosis, ASD atrial septal defect, AVSD atrioventricular septal defect, BAV bicuspid aortic valve, Coa coarctation of the aorta, DIVC dilated inferior vena cava, DORV double outlet right ventricle, E embryonic day, EA Epstein’s anomaly, EH enlarged heart, ND not determined, PDA patent ductus arteriosus, PFO persistence of foramen ovale, PTA persistent truncus arteriosus, PulAH pulmonary artery hypoplasia, SAR subaortic ridge, SDK septal dyskinesis, TA tricuspid atresia, SVC/CS abnormal drainage of superior vena cava to coronary sinus, TAAD thoracic aortic aneurysm and/or aortic dissection, TGA transposition of the great arteries, UnD unpublished data (Dr. CS Rutland and SL), VSD ventricular septal defect