Whereas Klf13 heterozygote mice have no detectable cardiac defects, loss of a Klf13 allele in Tbx5 heterozygote mice significantly increases the penetrance of TBX5-dependent cardiac abnormalities including atrial, atrial-ventricular and ventricular septal defects.
As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defectnot associated with forelimb malformation in the Chinese Han population.
In the autosomal dominant Holt-Oram syndrome, both atrial and ventricular septal defects are inherited in association with limb deformity as a result of mutations in the gene encoding the TBX5 transcription factor.