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A novel form of cell type-specific partial IFN-γR1 deficiency caused by a germ line mutation of the IFNGR1 initiation codon
- Source :
- Human Molecular Genetics. 19:434-444
- Publication Year :
- 2009
- Publisher :
- Oxford University Press (OUP), 2009.
-
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.
- Subjects :
- Mutation, Missense
Codon, Initiator
Biology
medicine.disease_cause
Cell Line
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Eukaryotic translation
Germline mutation
Species Specificity
Start codon
Genetics
medicine
Humans
Missense mutation
Genetic Predisposition to Disease
Child
Molecular Biology
Cells, Cultured
Germ-Line Mutation
Genetics (clinical)
Receptors, Interferon
030304 developmental biology
B-Lymphocytes
Mycobacterium Infections
0303 health sciences
Mutation
Articles
General Medicine
Fibroblasts
Phenotype
Molecular biology
030220 oncology & carcinogenesis
Interferon gamma receptor 1
Female
Signal transduction
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....dfe6c488d6413ca6ea9c8094df1754ba