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Common Variable Immunodeficiency Caused by FANC Mutations
- Source :
- Journal of clinical immunology. 37(5)
- Publication Year :
- 2016
-
Abstract
- Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4+ T cells were skewed toward CD45RO+ memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.
- Subjects :
- 0301 basic medicine
Adult
Male
Adolescent
T-Lymphocytes
Immunology
DNA Mutational Analysis
Receptors, Antigen, T-Cell
Gene mutation
Biology
Compound heterozygosity
medicine.disease_cause
Diagnosis, Differential
03 medical and health sciences
Young Adult
0302 clinical medicine
Fanconi anemia
Exome Sequencing
medicine
Immunology and Allergy
Humans
Genetic Predisposition to Disease
Child
Exome sequencing
Immunodeficiency
Genetic Association Studies
Mutation
Common variable immunodeficiency
Fanconi Anemia Complementation Group D2 Protein
Infant
medicine.disease
Flow Cytometry
FANCA
Fanconi Anemia Complementation Group Proteins
030104 developmental biology
Common Variable Immunodeficiency
Fanconi Anemia
Child, Preschool
Female
Biomarkers
030215 immunology
Subjects
Details
- ISSN :
- 15732592
- Volume :
- 37
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of clinical immunology
- Accession number :
- edsair.doi.dedup.....3f87129aa9a09053fcb71ee419a9e7f8