RESUMEN
Congenital heart defects represent a characteristic part of several genetic syndromes associated with chromosomal abnormalities such as 22q11.2 deletion syndrome; many genes located in this locus, mainly TBX1, are candidate genes for congenital heart defects. In our cohort of 27 subjects with congenital heart defect, both karyotype analysis and Fluorescence in situ hybridization (FISH) were performed. The TBX1 gene was sequenced in patients lacking chromosomal abnormalities. FISH analysis showed a de novo 22q11.2 deletion in two patients. The screening of TBX1 coding sequence identified a novel missense mutation c.569Câ¯>â¯A (p.P190Q) in six unrelated patients and detected two associated known single nucleotide polymorphisms; the c.664Câ¯>â¯T (rs2301558) in three patients and the c.420Tâ¯>â¯C (p.Phe140 Phe) (rs41298814) in one patient. Bioinformatic tools show that the novel missense mutation c.569Câ¯>â¯A could modify the function and the stability of the TBX1 protein. The c.569Câ¯>â¯A mutation was not found in 50 healthy controls. Ours results suggest a deleterious role of the c.569Câ¯>â¯A mutation and strengthen the hypothesis that this mutation might be responsible for the same phenotype spectrum as the 22q11.2 deletion syndrome.
