Activities of phospho-SMAD1/5/8 in three heterozygous variant groups (transfected with 0.5 μg wild-type plasmid and 0.5 μg variant plasmids) were approximately 30% lower than those in the 1.0 μg wild-type plasmid-transfected group, while the activities were approximately 20% higher than those in the 0.5 μg wild-type plasmid-transfected group (p < 0.0001; Figure 3E,F), suggesting that haploinsufficiency may represent the genetic mechanism in BMPR2-associated nonsyndromic oligodontia. This evidence concerns the gene SMAD1 and Oligodontia.