Indeed, haploinsufficiency of Tbx5 in mice reasonably phenocopies the hallmarks of HOS, including the asymmetric bilateral upper limb, frequent ASDs and VSDs, and abnormal cardiac electrophysiology, possibly due to poor formation of the conduction system (Bruneau et al. 2001; Moskowitz et al. 2007), as well as impaired cardiac relaxation (Zhu et al. 2008). Here, TBX5 is linked to Holt-Oram syndrome.