Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations

摘要: Mutations involving gains of glycosylation have been considered rare, and the pathogenic role new carbohydrate chains has never formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous respect a missense mutation in IFNGR2 creating N-glycosylation site IFNγR2 chain. The resulting additional moiety was both necessary sufficient abolish cellular response IFNγ. then searched Human Gene Mutation Database for potential gain-of-N-glycosylation mutations; 10,047 mutations 577 genes encoding proteins trafficked through secretory pathway, we 142 candidate (∼1.4%) 77 (∼13.3%). Six mutant bore N-linked moieties. Thus, an unexpectedly high proportion that cause human genetic might lead creation sites. Their effects may be direct consequence addition carbohydrate.