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Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome
Autoimmune Lymphoproliferative Syndrome (ALPS), commonly caused by mutations in the FAS gene, is a disease with variable penetrance. Subjects may be asymptomatic, or they may present with lymphadenopathy, splenomegaly, cytopenias, or malignancy. Prompt recognition of ALPS is needed for optimal manag...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012668/ https://www.ncbi.nlm.nih.gov/pubmed/33816397 http://dx.doi.org/10.3389/fped.2021.624116 |
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author | Gaefke, Claudia L. Metts, Jonathan Imanirad, Donya Nieves, Daime Terranova, Paola Dell'Orso, Gianluca Gambineri, Eleonora Miano, Maurizio Lockey, Richard F. Walter, Jolan Eszter Westermann-Clark, Emma |
author_facet | Gaefke, Claudia L. Metts, Jonathan Imanirad, Donya Nieves, Daime Terranova, Paola Dell'Orso, Gianluca Gambineri, Eleonora Miano, Maurizio Lockey, Richard F. Walter, Jolan Eszter Westermann-Clark, Emma |
author_sort | Gaefke, Claudia L. |
collection | PubMed |
description | Autoimmune Lymphoproliferative Syndrome (ALPS), commonly caused by mutations in the FAS gene, is a disease with variable penetrance. Subjects may be asymptomatic, or they may present with lymphadenopathy, splenomegaly, cytopenias, or malignancy. Prompt recognition of ALPS is needed for optimal management. We describe a multi-generational cohort presenting with clinical manifestations of ALPS, and a previously unreported heterozygous missense variant of uncertain significance in FAS (c.758G >T, p.G253V), located in exon 9. Knowledge of the underlying genetic defect permitted prompt targeted therapy to treat acute episodes of cytopenia. This cohort underscores the importance of genetic testing in subjects with clinical features of ALPS and should facilitate the reclassification of this variant as pathogenic. |
format | Online Article Text |
id | pubmed-8012668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80126682021-04-02 Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome Gaefke, Claudia L. Metts, Jonathan Imanirad, Donya Nieves, Daime Terranova, Paola Dell'Orso, Gianluca Gambineri, Eleonora Miano, Maurizio Lockey, Richard F. Walter, Jolan Eszter Westermann-Clark, Emma Front Pediatr Pediatrics Autoimmune Lymphoproliferative Syndrome (ALPS), commonly caused by mutations in the FAS gene, is a disease with variable penetrance. Subjects may be asymptomatic, or they may present with lymphadenopathy, splenomegaly, cytopenias, or malignancy. Prompt recognition of ALPS is needed for optimal management. We describe a multi-generational cohort presenting with clinical manifestations of ALPS, and a previously unreported heterozygous missense variant of uncertain significance in FAS (c.758G >T, p.G253V), located in exon 9. Knowledge of the underlying genetic defect permitted prompt targeted therapy to treat acute episodes of cytopenia. This cohort underscores the importance of genetic testing in subjects with clinical features of ALPS and should facilitate the reclassification of this variant as pathogenic. Frontiers Media S.A. 2021-03-18 /pmc/articles/PMC8012668/ /pubmed/33816397 http://dx.doi.org/10.3389/fped.2021.624116 Text en Copyright © 2021 Gaefke, Metts, Imanirad, Nieves, Terranova, Dell'Orso, Gambineri, Miano, Lockey, Walter and Westermann-Clark. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Gaefke, Claudia L. Metts, Jonathan Imanirad, Donya Nieves, Daime Terranova, Paola Dell'Orso, Gianluca Gambineri, Eleonora Miano, Maurizio Lockey, Richard F. Walter, Jolan Eszter Westermann-Clark, Emma Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome |
title | Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome |
title_full | Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome |
title_fullStr | Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome |
title_full_unstemmed | Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome |
title_short | Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome |
title_sort | case report: a novel pathogenic missense mutation in fas: a multi-generational case series of autoimmune lymphoproliferative syndrome |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012668/ https://www.ncbi.nlm.nih.gov/pubmed/33816397 http://dx.doi.org/10.3389/fped.2021.624116 |
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