Disease monogenic

Keywords FoUide-stimulating hormone gain of function gonadotropin-releasing hormone (GnRHR) G protein-coupled receptor loss of function luteinizing hormone melanocortin monogenic disease parathyroid hormone rhodopsin thyrotropin. 

While certain behavioral and nonbehavioral diseases are believed to be monogenic, diseases such as Huntington s, cystic fibrosis, Marfan, and Hirschsprung result in the specified disease, and the outward appearance or result (phenotype) of the disease varies between individuals. For instance, for Marfan syndrome, there is a level below which the mutant protein does not exhibit itself in an outward manner. Most of these diseases have modifier genes that cause modifications in the outward demonstration of the disease and play a key role in the clinical symptoms. Further, the particular metabolic pathways are often varied, with several of the steps being important and the importance of each mechanistic pathway may differ with every individual. 

As noted earlier, there are probably few single gene-associated, or monogenic, diseases and most involve a number of genes. This latter group comprises complex or multifactorial diseases, which are called QTL disorders or diseases. 

Table 21.3 shows the clinical studies that have been conducted worldwide, with their different applications, showing that therapies intended for monogenic disease treatment are the second most assessed group, after therapies for tumor treatment. The most used vectors in gene therapy clinical studies are viral vectors (68%), and among those, retroviruses and adenoviruses are the viruses of choice. Synthetic vectors were used in 25% of the studies performed, and about 16% correspond to the use of naked plasmid DNA (Table 21.4). 

Table 2 Monogenic diseases phase I and II ongoing gene therapy clinical trials as of February 1, 2001...

Porteus, M. H., Connelly, J. P, Pruett, S. M. A look to future directions in gene therapy research for monogenic diseases. PLoS Genet. 2006,2, el33. 

TABLE 7.1-2. Disease Targets for Gene Therapy Monogenic Diseases... 

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