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A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency
Svere combined immunodeficiencies (SCID) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. They are defined by the absence of autologous T cells and the presence of an intrinsic or extrinsic defect in the B-cell compartment. In t...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Fondazione Ferrata Storti
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849581/ https://www.ncbi.nlm.nih.gov/pubmed/31919089 http://dx.doi.org/10.3324/haematol.2019.230250 |
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author | Lagresle-Peyrou, Chantal Olichon, Aurélien Sadek, Hanem Roche, Philippe Tardy, Claudine Da Silva, Cindy Garrigue, Alexandrine Fischer, Alain Moshous, Despina Collette, Yves Picard, Capucine Casanova, Jean Laurent André, Isabelle Cavazzana, Marina |
author_facet | Lagresle-Peyrou, Chantal Olichon, Aurélien Sadek, Hanem Roche, Philippe Tardy, Claudine Da Silva, Cindy Garrigue, Alexandrine Fischer, Alain Moshous, Despina Collette, Yves Picard, Capucine Casanova, Jean Laurent André, Isabelle Cavazzana, Marina |
author_sort | Lagresle-Peyrou, Chantal |
collection | PubMed |
description | Svere combined immunodeficiencies (SCID) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. They are defined by the absence of autologous T cells and the presence of an intrinsic or extrinsic defect in the B-cell compartment. In three newborns presenting with frequent infections and profound leukopenia, we identified a private, heterozygous mutation in the RAC2 gene (p.G12R). This mutation was de novo in the index case, who had been cured by hematopoietic stem cell transplantation but had transmitted the mutation to her sick daughter. Biochemical assays showed that the mutation was associated with a gain of function. The results of in vitro differentiation assays showed that RAC2 is essential for the survival and differentiation of hematopoietic stem/progenitor cells. Therefore, screening for RAC2 gain-offunction mutations should be considered in patients with a SCID phenotype and who lack a molecular diagnosis. |
format | Online Article Text |
id | pubmed-7849581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-78495812021-02-03 A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency Lagresle-Peyrou, Chantal Olichon, Aurélien Sadek, Hanem Roche, Philippe Tardy, Claudine Da Silva, Cindy Garrigue, Alexandrine Fischer, Alain Moshous, Despina Collette, Yves Picard, Capucine Casanova, Jean Laurent André, Isabelle Cavazzana, Marina Haematologica Article Svere combined immunodeficiencies (SCID) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. They are defined by the absence of autologous T cells and the presence of an intrinsic or extrinsic defect in the B-cell compartment. In three newborns presenting with frequent infections and profound leukopenia, we identified a private, heterozygous mutation in the RAC2 gene (p.G12R). This mutation was de novo in the index case, who had been cured by hematopoietic stem cell transplantation but had transmitted the mutation to her sick daughter. Biochemical assays showed that the mutation was associated with a gain of function. The results of in vitro differentiation assays showed that RAC2 is essential for the survival and differentiation of hematopoietic stem/progenitor cells. Therefore, screening for RAC2 gain-offunction mutations should be considered in patients with a SCID phenotype and who lack a molecular diagnosis. Fondazione Ferrata Storti 2020-01-09 /pmc/articles/PMC7849581/ /pubmed/31919089 http://dx.doi.org/10.3324/haematol.2019.230250 Text en Copyright© 2021 Ferrata Storti Foundation http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Lagresle-Peyrou, Chantal Olichon, Aurélien Sadek, Hanem Roche, Philippe Tardy, Claudine Da Silva, Cindy Garrigue, Alexandrine Fischer, Alain Moshous, Despina Collette, Yves Picard, Capucine Casanova, Jean Laurent André, Isabelle Cavazzana, Marina A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
title | A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
title_full | A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
title_fullStr | A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
title_full_unstemmed | A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
title_short | A gain-of-function RAC2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
title_sort | gain-of-function rac2 mutation is associated with bone marrow hypoplasia and an autosomal dominant form of severe combined immunodeficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849581/ https://www.ncbi.nlm.nih.gov/pubmed/31919089 http://dx.doi.org/10.3324/haematol.2019.230250 |
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