A pathogenic variant in the fifth exon of TBX5 causing a glycine to arginine substitution (c.373G>A; p.G125R) in the T-box domain was found in a Dutch, atypical HOS family.15 In this family, affected members show HOS symptoms such as mild skeletal abnormalities and septal defects, as well as atypical early onset paroxysmal AF. Here, TBX5 is linked to Holt-Oram syndrome.