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

Frontiers in Pediatrics

article

Claudia L. Gaefke¹  Jolan Eszter Walter²  Emma Westermann-Clark¹  Jonathan Metts⁴  Donya Imanirad¹  Daime Nieves²  Paola Terranova⁵  Gianluca Dell'Orso⁵  Eleonora Gambineri⁶  Maurizio Miano⁵  Richard F. Lockey¹ 

[1] Department of Medicine, University of South Florida, United States;Department of Pediatrics, University of South Florida, United States;Massachusetts General Hospital and Harvard Medical School, United States;Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, United States;Hematology Unit, IRCCS Istituto Giannina Gaslini;Meyer Children's Hospital

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

DOI  :  10.3389/fped.2021.624116

学科分类：社会科学、人文和艺术（综合）

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