Abstract:
:Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Vogt G,Chapgier A,Yang K,Chuzhanova N,Feinberg J,Fieschi C,Boisson-Dupuis S,Alcais A,Filipe-Santos O,Bustamante J,de Beaucoudrey L,Al-Mohsen I,Al-Hajjar S,Al-Ghonaium A,Adimi P,Mirsaeidi M,Khalilzadeh S,Rosenzweig S,ddoi
10.1038/ng1581keywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
692-700issue
7eissn
1061-4036issn
1546-1718pii
ng1581journal_volume
37pub_type
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