DNA mutations are the cause of many human diseases and they are also the reason for natural differences among individuals by affecting the structure, function, interactions, and other properties of DNA and expressed proteins. Some diseases are caused by mutations in several genes, while others are caused by defects in a single gene (monogenic diseases). Here we focus on two monogenic diseases: (a) the Snyder-Robinson Syndrome (SRS) which is a rare mental retardation disorder caused by missense mutations in spermine synthase (SMS) and (b) the Rett syndrome (RTT) which is a brain disorder that is linked with mutations in MeCP2 protein, and it is estimated to affect 1 in 8,500 females. We demonstrate that the vast majority of mutations do not directly affect the functionality of the corresponding protein, but rather alter its stability and affinity. This prompted us to seek small molecules which target the mutant protein and upon the binding restore its wild type characteristics. The computational findings are experimentally verified.