Case Report: A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome

Frontiers in Pediatrics

Jonathan Metts¹  Claudia L. Gaefke²  Richard F. Lockey²  Donya Imanirad²  Emma Westermann-Clark³  Daime Nieves⁴  Jolan Eszter Walter⁵  Paola Terranova⁶  Maurizio Miano⁶  Gianluca Dell'Orso⁶  Eleonora Gambineri⁷ 

[1] Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States;Department of Medicine, University of South Florida, Tampa, FL, United States;Department of Medicine, University of South Florida, Tampa, FL, United States;Department of Pediatrics, University of South Florida, Saint Petersburg, FL, United States;Department of Pediatrics, University of South Florida, Saint Petersburg, FL, United States;Department of Pediatrics, University of South Florida, Saint Petersburg, FL, United States;Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Hematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy;NEUROFARBA, Meyer Children's Hospital, Florence, Italy;

关键词: ALPS (autoimmune lymphoproliferative syndrome);    novel mutation;    Fas;    cytopenia;    lymphoproliferation;   

DOI  :  10.3389/fped.2021.624116

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY