BAD OMIMID 611363(ATRIALSEPTALDEFECT4) None None
|17668378||Kirk et al. (2007) identified a c.583C>T transition in the TBX20 gene in a family in which 6 members in 3 generations had a history of various cardiac anomalies (ASD, mitral valve disease, pulmonary hypertension and cardiomyopathy). The c.583C>T is a nonsense mutation (Q195X) resulting in a truncated TBX20 protein that lacks the C-terminal trans activation and trans repression domains. The c.583C>T transition was not seen in >300 controls. This mutation resulted in reduced transcriptional activation and the inability to induce cardiac tissue formation in frogs and seems to be consistent with loss of function. This group also reports a missense mutation in a family with cardiac anomalies that showed increased DNA binding affinity and possible gain of function mechanism.|
Mutations in TBX20 have been identified in families with atrial septal defect (ASD) and other congenital heart disease, but not in individuals with conduction defects or noncardiac abnormalities. Liu et al (2008, PMID:18834961) report three patients with cardiac anomalies and missense mutations; two were de novo and one was present in a normal sibling and mother. Functional studies were not performed. Posch et al. (2010, PMID: 19762328) identified a c.374C>G transversion in exon 2 of the TBX20 gene in 3 members of a Lebanese family with heart defects (ASD and cardiac valve defects). The c.374C>G results in a I121M missense mutation. The mutation was not found in 2 unaffected family members, in 680 control alleles, or in 218 control probands from Lebanon. Functional analysis (transcriptional activity via luciferase assay) revealed that the I121M mutant had significantly enhanced transcriptional activity, suggesting that it is a gain-of-function allele.