TBX5 and Holt-Oram syndrome: Al-Qattan et al. reviewed the genotype–phenotype correlation in typical HOS patients resulting from missense mutations of TBX5, concluding that most of the mutations were found in the DNA-binding domain of the gene, thus affecting the interaction with other transcription factors regulating the embryological development of the heart and limbs (such as GATA4 or NKX2-5) and causing loss of function [40].