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 TITLE=Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome JOURNAL=Frontiers in Pediatrics VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.624116 DOI=10.3389/fped.2021.624116 ISSN=2296-2360 ABSTRACT=

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.