Courtesy of Michael Conn
Above are the loci for all known naturally occurring mutants of the human gonadotropin releasing hormone receptor (GnRHR) identified from patients with hypogonadotropic hypogonadism (HH). The vast majority of point mutations can be functionally rescued through the use of a pharmacological chaperone. Some others had not been attempted. Twelve mutations identified in yellow letters result in modest charge changes. A smaller number result in other changes to the tertiary structure. Also shown for reference is Lys191 (red circle), an amino acid present in primates, but not in rodents.
Gene therapy has been a major focus for research into treating a number of diseases caused by receptor protein mutations. But a potentially more direct therapy is emerging with the discovery of small molecules that restore correct function to mutant receptor proteins, without attempting to change the primary sequence.
"This is going to be an important area for ...
