In humans, HOS patients can present with softtissue abnormalities that are not associated with skeletal defects (Newbury-Ecob, ;Newbury-Ecob et al., 1996; Spranger et al., 1997) consistent with theobservations that, despite the widespread soft tissue defects produced in our mousemodels following deletion of Tbx5/4, the skeleton could beunaffected. This evidence concerns the gene TBX5 and Holt-Oram syndrome.