title: Gain-of-glycosylation mutations.
abstract: Disease-causing missense (and other in-frame) mutations can exert their deleterious effects at the cellular level through multiple mechanisms. A pathogenic mechanism involves the addition of a novel N-linked glycan. Up to 1.4% of known disease-causing missense mutations are predicted to give rise to gains-of-glycosylation. For some of these mutations, the novel glycans have been shown to be both necessary and sufficient to account for the deleterious impact of the mutation. The chemical complementation of cells from patients in vitro with various modifiers of glycosylation has been demonstrated and raises the possibility of specific chemical treatments for patients bearing gain-of-glycosylation mutations.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, INSERM, U550, Paris 75015, France. vogt@necker.fr
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.forename: Benoît
authors.initials: B
authors.lastname: Vogt
authors.forename: Nadia
authors.initials: N
authors.lastname: Chuzhanova
authors.forename: Karin
authors.initials: K
authors.lastname: Julenius
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D004194:Disease; D005947:Glucose / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D009154:Mutation / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D005947:Glucose; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor