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.
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.
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.
Through biological and in silico analyses, our study suggests an association between SIX1/EYA1 mutations and cardiovascular malformations, SIX1/EYA1 mutations might be partially responsible for CTDs.
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).
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.
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).
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.
Our analyses revealed 28 candidate variants in 27 genes, including 17 genes not previously associated with a human CVM disorder, and revealed diverse patterns of inheritance among LOF carriers, including 9 confirmed de novo variants in both novel and newly described human CVM candidate genes (ACVR1, JARID2, NR2F2, PLRG1, SMURF1) as well as established syndromic CVM genes (KMT2D, NF1, TBX20, ZEB2).
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.
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.
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.
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.
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.
Animal studies have shown that knockout of the transforming growth factor beta-2 (TGFβ2) gene results in diverse cardiovascular malformations and that its unregulated expression is involved in the pathogenesis of heart defects.
Maternal phenylketonuria (MPKU) is a syndrome including cardiovascular malformations (CVMs), microcephaly, intellectual impairment, and small size for gestational age, caused by in-utero exposure to elevated serum phenylalanine (Phe) due to PKU in the mother.
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.
The results suggest that cardiac phenotypes are very variable in patients with the terminal deletion of chromosome 4q and that haploinsufficiency of the dHAND is not necessarily associated with CVMs.
Most WBS patients have a >1 Mb deletion on one of their chromosomes 7 in q11 but except for elastin, whose haploinsufficiency causes the cardiovascular malformations, it is unknown which genes in the deletion area contribute to the phenotype.
Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice.