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RAG1 reversion mosaicism in a patient with Omenn syndrome.
- Source :
-
Journal of clinical immunology [J Clin Immunol] 2014 Jul; Vol. 34 (5), pp. 551-4. Date of Electronic Publication: 2014 May 10. - Publication Year :
- 2014
-
Abstract
- Purpose: To identify mechanisms of disease in a child born to consanguineous parents, who presented with Omenn syndrome (OS) and was found to carry a heterozygous RAG1 mutation in peripheral blood DNA.<br />Methods: Mutation analysis was performed on whole blood and buccal swab DNA. Recombination activity of the mutant RAG1 protein and diversity of T cell repertoire were tested.<br />Results: Apparent heterozygosity for a novel, functionally null RAG1 mutation in peripheral blood DNA from a patient with OS was shown to be secondary to true somatic reversion. Analysis of T cell repertoire demonstrated expression of various TCRBV families, but an overall restricted pattern.<br />Conclusions: This is the first case of true somatic reversion of a RAG1 mutation in a patient with OS. The reversion event likely occurred at a stage where only a limited pool of T cell progenitors capable of performing V(D)J recombination could be generated. This work emphasizes the importance of performing functional studies to investigate the significance of novel genetic variants, and to consider somatic reversion as a possible disease modifier in SCID.
- Subjects :
- B-Lymphocytes immunology
B-Lymphocytes pathology
DNA Mutational Analysis
Genotype
Hematopoietic Stem Cell Transplantation
Heterozygote
Homeodomain Proteins blood
Humans
Infant
Male
Severe Combined Immunodeficiency immunology
Severe Combined Immunodeficiency pathology
Severe Combined Immunodeficiency therapy
T-Lymphocytes immunology
T-Lymphocytes pathology
Transposases blood
Homeodomain Proteins genetics
Mosaicism
Severe Combined Immunodeficiency genetics
Transposases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2592
- Volume :
- 34
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24817258
- Full Text :
- https://doi.org/10.1007/s10875-014-0051-2