Figure 1

Model of the potential impact of Nonsense-Mediated Decay (NMD) on protein expression. Activation of the NMD pathway results in the degradation of susceptible mutant transcripts, leaving only the remaining wild-type allele that produces normal BMPR2 protein. The individual may be susceptible to disease because protein amount is quantitatively but not qualitatively reduced, resulting in 'haploinsufficiency'. Mutant RNA transcripts that are resistant to NMD may result in a mutant protein with abnormal function, including the disruption of activity by normal BMPR2 protein produced by the normal allele. The potential deleterious effect of this qualitatively but not quantitatively altered protein can result in 'dominant negative' effects, and even greater susceptibility to disease.