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

[holt-oram syndrome]

Congenital heart diseases are the most frequent birth defects and are commonly associated with skeletal malformations . Mutations in the TBX 5 gene , a T -box transcription factor located on chromosome 12 q 24 .1 , have been demonstrated to be the underlying molecular alteration in individuals with different congenital cardiac disorders , notably the Holt-Oram syndrome .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 TBX 5 mutational analysis performed by direct sequencing .We detected a new TBX 5 missense mutation (V 26 3 M ) 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 .These new data extend our clinical and molecular knowledge of TBX 5 gene mutations and also raise interesting questions about the phenotype heterogeneity regarding these gene alterations .