TBX5 and atrial septal defect: Patient HH17, a woman with ASD and triphalangeal thumbs (Figure 1A), had a previously described pathogenic mutation (c.835C > T/ p.R279X) that does not affect the TBX5-binding domain, but causes the loss of its C-terminal portion (Li et al., 1997), and is considered a hotspot mutation (Heinritz et al., 2005b).