Because of the wide phenotypic variability found in the HOS patients, we screened for mutations in the TBX5, GATA4 and NKX2.5 genes in patients presenting with classical HOS, classical HOS with feet anomalies, patients with isolated upper-limb malformations, and patients with isolated heart defects. The gene discussed is NKX2-5; the disease is Holt-Oram syndrome.