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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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