Kirk et al. (2007) identified 2 families with congenital heart defects, in which affected individuals displayed a complex spectrum of cardiac developmental abnormalities, including defects in septation, chamber growth, and valvulogenesis, and heterozygous mutation in the TBX20 gene. ... Kirk et al. (2007) identified 2 families with congenital heart defects, in which affected individuals displayed a complex spectrum of cardiac developmental abnormalities, including defects in septation, chamber growth, and valvulogenesis, and heterozygous mutation in the TBX20 gene. The proband of the first family had ASD, which was corrected surgically in early childhood. Her grandmother had a small ventriculoseptal defect (VSD), and her mother had a large patent foramen ovale (PFO) with a permanent left-to-right blood shunt. Cardiac valves and left ventricular function were normal in all individuals. The proband of the second family had a small ASD and mild coarctation of the aorta. At age 31 years he underwent percutaneous device closure of the ASD. He also had mild to moderate pulmonary hypertension diagnosed on cardiac catheterization at age 7 months and 6 years, although this resolved. Reduced left ventricular function was also identified by echocardiography and cardiac catheterization in childhood, and this persisted into adulthood; at age 32 years, echocardiogram demonstrated a mildly dilated left ventricle with mild global impairment of systolic function. The mother of the proband had marked mitral valve prolapse with mild regurgitation, dilated cardiomyopathy, and apicolateral hypertrophy. A half sister of the mother was scheduled for repair of a septal defect when she died in a vehicle accident during her 20s. An older sister of the proband died at age 11 months because of congenital mitral valve stenosis associated with a small left ventricle and endocardial fibroelastosis. Another sister died at age 7 years of right heart failure due to severe primary pulmonary hypertension. A man from the earliest of 3 generations in this family, deceased at the time of report, had mitral valve disease.
In 2 families with congenital heart defects, Kirk et al. (2007) identified heterozygous mutation in the TBX20 gene. Affected members of the first family carried an ile152-to-met (I152M) mutation (I152M; 606061.0001); affected members of the second family carried ... In 2 families with congenital heart defects, Kirk et al. (2007) identified heterozygous mutation in the TBX20 gene. Affected members of the first family carried an ile152-to-met (I152M) mutation (I152M; 606061.0001); affected members of the second family carried a gln195-to-stop mutation (Q195X; 606061.0002). Posch et al. (2010) analyzed the TBX20 gene in 170 patients with ostium secundum atrial septal defects and identified heterozygosity for a missense mutation (I121M; 606061.0003) in a male proband with a cribriform ostium secundum ASD and 3 distinct perforations in the atrial septum. The mutation was also present in heterozygosity in his mother and sister, who each had a large patent foramen ovale with permanent shunt. No DNA was available from the maternal grandmother, who had undergone surgical replacement of the aortic and mitral valves at 35 years of age and died at age 55 years. The mutation was not found in the proband's 2 unaffected brothers, in 680 control alleles, or in 218 control probands from Lebanon. Structural and functional analysis showed that the mutant protein had a more dynamic structure than wildtype and significantly enhanced transcriptional activity. Posch et al. (2010) suggested that ostium secundum atrial septal defects may be associated with gain-of-function as well as loss-of-function mutations.