Identification of TBX5 mutations in a series of 94 patients with Tetralogy of Fallot

摘要: Tetralogy of Fallot (TOF) (OMIM #187500) is the most frequent conotruncal congenital heart defect (CHD) with a range intra- and extracardiac phenotypes. TBX5 transcription factor well-defined roles in forelimb development, mutations are associated Holt-Oram syndrome (HOS) (OMIM#142900). Here we report on screening 94 TOF patients for TBX5, NKX2.5 GATA4 genes. We identified two heterozygous TBX5. One mutation was detected Moroccan patient TOF, large ostium secundum atrial septal complete atrioventricular block, features HOS including bilateral triphalangeal thumbs fifth finger clinodactyly. This carried previously described de novo, stop codon (p.R279X) located exon 8 causing premature truncated protein. In second from Italy progressive arrhythmic changes ECG, maternally inherited novel 9, which caused substitution serine leucine at amino acid position 372 (p.S372L, c.1115C>T). The mother's clinical evaluation demonstrated ventricular extrasystoles an aneurysm. Physical examination radiographs hands showed no apparent skeletal defects either child or mother. Molecular p.S372L gain-of-function phenotype. also review literature co-occurrence HOS, highlighting its relevance. first systematic (2.1%) patients.