Tetralogy of Fallot (TBX1)
| Dred_ID | RD00027 |
| OMIM ID | 187500 |
| Disease name | Tetralogy of Fallot |
| Alternative names | TOF |
| Category | Genetic diseases, Rare diseases, Fetal diseases |
| Phenotype | GARD: Tetralogy of Fallot is a complex congenital heart defect characterized by a large ventricular septal defect (hole between the right and left ventricles), pulmonary stenosis (narrowing of the valve and artery that connect the heart with the lungs), an overriding aorta (the aorta - the artery that carries oxygen-rich blood to the body - is shifted over the right ventricle and ventricular septal defect, instead of coming out only from the left ventricle), and right ventricular hypertrophy (the muscle of the right ventricle is thicker than usual). Tetralogy of Fallot causes low oxygen levels in the blood, which can lead to cyanosis (a bluish-purple color to the skin). The cause of this condition is unknown. Treatment involves surgery to repair the heart defects. Sometimes more than one surgery is needed. MalaCards based summary: Tetralogy of Fallot, also known as tof, is related to congenital heart defects, multiple types, 4 and heart septal defect. An important gene associated with Tetralogy of Fallot is JAG1 (Jagged Canonical Notch Ligand 1), and among its related pathways/superpathways are Mesodermal Commitment Pathway and Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers. The drugs Eplerenone and Mineralocorticoids have been mentioned in the context of this disorder. Affiliated tissues include heart, brain and skin, and related phenotypes are abnormal nasal morphology and intrauterine growth retardation. |
| Miscellaneouse | Age of onset: Antenatal,Neonatal; |
| Prevalence | Prevalence: 1-5/10000 (Europe),1-5/10000 (Austria),1-5/10000 (Belgium) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Weak |
| Gene symbol | TBX1 |
| Alias symbols | DGS; TGA; VCF; CAFS; CTHM; DGCR; DORV; VCFS; TBX1C; CATCH22 |
| Gene name | T-box transcription factor 1 |
| Gene map locus | 22q11.21; chr22:19,756,703-19,783,593(+) |
| Ensembl Gene ID | ENSG00000184058 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. |
| Repeat unit | GCN |
| Normal repeat copies | 15 |
| Pathogenic repeat copies | ≥25 |
| Gene | TBX1 |
| Repeat location | CDS |
| Chromosome locus | chr22:19766763-19766809 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | In a Turkish female patient with tetralogy of Fallot, Rauch et al. (2010) identified a heterozygous 30-bp duplication in the TBX1 gene on chromosome 22q11.2 (602054.0006). She had facial asymmetry, scoliosis, absent pulmonary vein, isolated left pulmonary artery, ventricular septal defect, and normal cognitive development. She did not have the facial gestalt of 22q11.2 deletion syndrome. The insertion was shown to result in the expansion of a polyalanine tract, which caused decreased transcriptional activity and cytoplasmic aggregation of the protein in cellular studies. |
| Pathway annotation | Reactome, KEGG |
| PMID | 19948535 |
| Authors | Rauch R, Hofbeck M, Zweier C, Koch A, et al. |
| Title | Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot |
| Journal | J. Med. Genet. |
| Year | 2010 |