The Zic3 mouse model provides a novel tool to dissect the mechanistic underpinnings of conduction system patterning and dysfunction and its relationship to cardiovascular malformations, making it a promising model to improve understanding and risk assessment in the clinical arena.
In humans, loss-of-function mutations in ZIC3 cause isolated cardiovascular malformations and X-linked heterotaxy, a disorder with abnormal left-right asymmetry of organs.
Human Filamin A gene (FLNA) mutations are associated with classical X-linked bilateral periventricular nodular heterotopia (PNH), featuring contiguous heterotopic nodules, mega cisterna magna, cardiovascular malformations and epilepsy.
Furthermore, the mutation abolished the synergistic activation between HAND1 and GATA4, another crucial cardiac transcription factors that has been associated with various congenital cardiovascular malformations and DCM.
Overall, our findings indicate that ADAP2 has a role in heart development, and might be a reliable candidate gene for the occurrence of cardiovascular malformations in patients with NF1 microdeletion and, more generally, for the occurrence of a subset of congenital heart defects.
Furthermore, the mutation abolished the synergistic activation between HAND1 and GATA4, another crucial cardiac transcription factors that has been associated with various congenital cardiovascular malformations and DCM.
Vascular malformations have a prevalence of 19%, with further evidence that complex cardiovascular malformations may be related to PTEN mutations; 31% of patients present hamartomas.
Within our clinical cohort, we also observed heterozygous LOF variants in JARID2 and SMAD1 in individuals with cardiac phenotypes, and collectively, carriers of LOF variants in our candidate genes had a four times higher odds of having CVM (odds ratio = 4.0, 95% confidence interval 2.5-6.5).
The diagnostic accuracy of 320-row CT in complex CHD was 99.4% for intracardiac cardiovascular malformations, 99.8% for extracardiac cardiovascular malformations, and 100% for other malformations.
The LIM homeodomain transcriptor factor ISL1 is a marker for undifferentiated cardiac progenitor cells that give rise to both the right ventricle and the inflow and outflow tracts, which are affected by several cardiovascular malformations.
Mice lacking expression of the elastic fiber genes elastin ( Eln<sup>-/-</sup>), fibulin-4 ( Efemp2<sup>-/-</sup>), or lysyl oxidase ( Lox<sup>-/-</sup>) die at birth with severe cardiovascular malformations.
Mice lacking expression of the elastic fiber genes elastin ( Eln<sup>-/-</sup>), fibulin-4 ( Efemp2<sup>-/-</sup>), or lysyl oxidase ( Lox<sup>-/-</sup>) die at birth with severe cardiovascular malformations.
PM<sub>10</sub> levels were positively associated with the risks of atrial septal defect (aORs ranging from 1.29 to 2.17), patent ductus arteriosus [aORs = 1.54, 1.63; 95% confidence intervals (CIs): 1.17, 2.23; 1.06, 3.24], overall fetal cardiovascular malformations (aOR = 1.28; 95% CI: 1.03, 1.61), ventricular septal defect (aOR = 1.19; 95% CI: 1.00, 1.43), and tetralogy of Fallot (aOR = 1.44; 95% CI: 1.01, 2.19) in the various observed periods scaled by 10 d or 1 mo in the first and second gestation months.
Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
Here we have investigated whether variants in NODAL are present in patients with heterotaxy and/or isolated cardiovascular malformations (CVM) thought to be caused by abnormal heart tube looping.
Within our clinical cohort, we also observed heterozygous LOF variants in JARID2 and SMAD1 in individuals with cardiac phenotypes, and collectively, carriers of LOF variants in our candidate genes had a four times higher odds of having CVM (odds ratio = 4.0, 95% confidence interval 2.5-6.5).
The LIM homeodomain transcriptor factor ISL1 is a marker for undifferentiated cardiac progenitor cells that give rise to both the right ventricle and the inflow and outflow tracts, which are affected by several cardiovascular malformations.
Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2.
De novo missense variants in CDK13 have been described as the cause of syndromic congenital heart defects in seven individuals ascertained from a large congenital cardiovascular malformations cohort.