A novel TBX5 missense mutation (V263M) in a family with atrial septal defects and postaxial hexodactyly

Background Congenital heart diseases are the most frequent birth defects and are commonly associated with skeletal malformations. Mutations in the TBX5 gene, a T-box transcription factor located on chromosome 12q24.1, have been demonstrated to be the underlying molecular alteration in individuals with different congenital cardiac disorders, notably the Holt–Oram syndrome. Methods Six members from a two-generation family from a consanguineous couple, which had atrial septal defects associated with postaxial hexodactyly in all extremities were clinically assessed and submitted to TBX5 mutational analysis performed by direct sequencing. Results We detected a new TBX5 missense mutation (V263M) in all four individuals studied with cardiac abnormalities. The genotype–phenotype correlations in light of unusual features are extensively discussed, as well as the possible significance of these atypical findings. Conclusions These new data extend our clinical and molecular knowledge of TBX5 gene mutations and also raise interesting questions about the phenotype heterogeneity regarding these gene alterations.