A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.
Nat Genet
; 21(4): 370-8, 1999 Apr.
Article
in En
| MEDLINE
| ID: mdl-10192386
ABSTRACT
The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sequence Deletion
/
Receptors, Interferon
/
Genetic Predisposition to Disease
/
Mycobacterium Infections
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
1999
Type:
Article
Affiliation country:
France