ArticleProceedings of the National Academy of Sciences of the United States of America2001
Somatic mosaicism in Wiskott--Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 153 citations in OpenAlex.
- Inborn Error of WAS Presenting with SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children.Journal of clinical immunology · 2024Article
- Unraveling facets of MECOM-associated syndrome: somatic genetic rescue, clonal hematopoiesis, and phenotype expansion.Blood advances · 2024Article
- Gene therapy for inborn errors of immunity: past, present and future.Nature reviews. Immunology · 2023Review
- Genetic Mosaicism as a Cause of Inborn Errors of Immunity.Journal of clinical immunology · 2021Review
- Reversion Mosaicism in Primary Immunodeficiency Diseases.Frontiers in immunology · 2021Review
- Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies.Frontiers in cell and developmental biology · 2021Review
- Somatic genetic rescue in Mendelian haematopoietic diseases.Nature reviews. Genetics · 2019Review
- Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome.Journal of clinical immunology · 2018Review
- A "late-but-fitter revertant cell" explains the high frequency of revertant mosaicism in epidermolysis bullosa.PloS one · 2018Article
- Revertant mosaicism in genodermatoses.Cellular and molecular life sciences : CMLS · 2017Review
- FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy.The Journal of clinical investigation · 2016Article
- Basophil activation by mosquito extracts in patients with hypersensitivity to mosquito bites.Cancer science · 2015Article
- Outcomes in two Japanese adenosine deaminase-deficiency patients treated by stem cell gene therapy with no cytoreductive conditioning.Journal of clinical immunology · 2015Article
- Signal Integration during T Lymphocyte Activation and Function: Lessons from the Wiskott-Aldrich Syndrome.Frontiers in immunology · 2015Review
- Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases.International journal of hematology · 2014Review
- A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells.Haematologica · 2013Article
- Rapid detection of intracellular p47phox and p67phox by flow cytometry; useful screening tests for chronic granulomatous disease.Journal of clinical immunology · 2013Article
- Clonal expansion of Epstein-Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions.International journal of hematology · 2012Article
- Decreased expression in nuclear factor-κB essential modulator due to a novel splice-site mutation causes X-linked ectodermal dysplasia with immunodeficiency.Journal of clinical immunology · 2011Article
- Revertant mosaicism in skin: natural gene therapy.Trends in molecular medicine · 2011Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Somatic mosaicism caused by in vivo reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. In most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott--Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.