@article {7746,
	title = {Comment to Santos et al., "hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype".},
	journal = {Gene},
	volume = {559},
	year = {2015},
	month = {2015 Mar 15},
	pages = {99-101},
	abstract = {<p>We performed molecular modeling analysis onto a novel mutation in the gene MVK, described by Santos et al., found to be causative of a severe form of Hyper-IgD/Mevalonate Kinase Deficiency. The mutation p.R277G, in our analysis, lowers the binding affinity for some enzyme{\textquoteright}s substrates. Interestingly, we found that p.R277G mutation inhibits binding of Isopentenyl Pyrophosphate (IPP) (binding free energy=0 kcal/mol), one of isoprenoids responsible for feedback-inhibition of MVK. IPP is known to be an activator of a specific class of T-cells and we can hypothesize that increased levels of this metabolite generate an aberrant immune system response. Indeed other experiments are needed to verify this hypothesis; however, this work demonstrates usefulness of molecular modeling in generating novel pathogenic hypothesis.</p>},
	keywords = {Fever, Humans, Immunoglobulin D, Male, Mutation, Missense, Phosphotransferases (Alcohol Group Acceptor)},
	issn = {1879-0038},
	doi = {10.1016/j.gene.2015.01.029},
	author = {Santos, Ruda de Luna Almeida and Crovella, Sergio and Celsi, Fulvio}
}
