title: A novel form of cell type-specific partial IFN-gammaR1 deficiency caused by a germ line mutation of the IFNGR1 initiation codon.
abstract: IFN-gammaR1 deficiency is a genetic etiology of Mendelian susceptibility to mycobacterial diseases, and includes two forms of complete recessive deficiency, with or without cell surface expression, and two forms of partial deficiency, dominant or recessive. We report here a novel form of partial and recessive Interferon gamma receptor 1 (IFN-gammaR1) deficiency, which is almost as severe as complete deficiency. The patient is homozygous for a mutation of the initiation codon (M1K). No detectable expression and function of IFN-gammaR1 were found in the patient's fibroblasts. However, IFN-gammaR1 expression was found to be impaired, but not abolished, on the EBV-transformed B cells, which could respond weakly to IFN-gamma. The mechanism underlying this weak expression involves leaky translation initiation at both non-AUG codons and the third AUG codon at position 19. It results in the residual expression of IFN-gammaR1 protein of normal molecular weight and function. The residual IFN-gamma signaling documented in this novel form of partial IFN-gammaR1 deficiency was not ubiquitous and was milder than that seen in other forms of partial IFN-gammaR1 deficiency, accounting for the more severe clinical phenotype of the patient, which was almost as severe as that of patients with complete deficiency.
authors.affiliation: These authors contributed equally to this work.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Kong
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Christophe
authors.initials: C
authors.lastname: Lamaze
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Carolina
authors.initials: C
authors.lastname: Prando
authors.forename: Anny
authors.initials: A
authors.lastname: Fortin
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Feinberg
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
authors.forename: Pauline
authors.initials: P
authors.lastname: Gonnord
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Pihkala-Saarinen
authors.forename: Mikko
authors.initials: M
authors.lastname: Arola
authors.forename: Petra
authors.initials: P
authors.lastname: Moilanen
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Matti
authors.initials: M
authors.lastname: Korppi
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D018387:Codon, Initiator; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020125:Mutation, Missense; D009164:Mycobacterium Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics*; D013045:Species Specificity; D000096743:Interferon gamma Receptor
chemical_list: D018387:Codon, Initiator; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor