TBX1 gene mutation screening in patients with non-syndromic Fallot tetralogy

Fallot tetralogy (FT) is the most frequently observed conotruncal heart defect (CTHD) and accompanies 15% of the 22q11 deletion syndromes, DiGeorge/ velocardiofacial (DGS/VCFS) syndromes. TBX1 is a gene located in the 22q11 region and has a role in neural crest migration and conotruncal development. The mouse Tbx1 locus shows 98% homology with TBX1. DGS/VCFS-like aortic arch abnormalities in the mouse were attributed to deletions in this locus. The T-box region, common to both mice and humans, is part of TBX1 with proven effects on heart outflow track anomalies. The role of TBX1 in non-syndromic CTHDs is still unclear. In this study, we screened the TBX1 gene T-box region exons in 50 FT patients without 22q11 deletion and in 50 healthy volunteers. Our study did not show any disease causing mutations, but one polymorphic change. These results do not support a major role of the T-box region in the etiology of isolated FT. Furthermore, this study also confirms that mouse cardiac-development study models do not always provide an explanation for human phenotype-genotype correlations.