TY - JOUR
T1 - Case Report
T2 - A Novel Pathogenic Missense Mutation in FAS: A Multi-Generational Case Series of Autoimmune Lymphoproliferative Syndrome
AU - Gaefke, Claudia L.
AU - Metts, Jonathan
AU - Imanirad, Donya
AU - Nieves, Daime
AU - Terranova, Paola
AU - Dell'Orso, Gianluca
AU - Gambineri, Eleonora
AU - Miano, Maurizio
AU - Lockey, Richard F.
AU - Walter, Jolan Eszter
AU - Westermann-Clark, Emma
N1 - Funding Information:
This research was partly funded by Johns Hopkins All Children’s Hospital (JHACH) Institutional Grant entitled Feasibility study to assess the role of T and B cells in refractory cytopenias in children (JEW), the Jeffrey Modell Foundation, Jeffrey Modell Diagnostic and Research Center at JHACH and the Robert A. Good Endowment at the University of South Florida. The Jeffrey Modell Foundation funds supported genetic testing. The JHACH Institutional Grant supported a larger study on autoimmune cytopenia, in which the ALPS subjects were enrolled.
Funding Information:
Alina Ramirez as liaison for the study who assisted with coordination of patient care. Maryssa Ellison and Sumai Gordon for research/sample coordination. Earle Trott for assistance with publication documents. Funding. This research was partly funded by Johns Hopkins All Children's Hospital (JHACH) Institutional Grant entitled Feasibility study to assess the role of T and B cells in refractory cytopenias in children (JEW), the Jeffrey Modell Foundation, Jeffrey Modell Diagnostic and Research Center at JHACH and the Robert A. Good Endowment at the University of South Florida. The Jeffrey Modell Foundation funds supported genetic testing. The JHACH Institutional Grant supported a larger study on autoimmune cytopenia, in which the ALPS subjects were enrolled.
Publisher Copyright:
© Copyright © 2021 Gaefke, Metts, Imanirad, Nieves, Terranova, Dell'Orso, Gambineri, Miano, Lockey, Walter and Westermann-Clark.
PY - 2021/3/18
Y1 - 2021/3/18
N2 - 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.
AB - 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.
KW - ALPS (autoimmune lymphoproliferative syndrome)
KW - Fas
KW - cytopenia
KW - lymphoproliferation
KW - novel mutation
UR - http://www.scopus.com/inward/record.url?scp=85103493075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103493075&partnerID=8YFLogxK
U2 - 10.3389/fped.2021.624116
DO - 10.3389/fped.2021.624116
M3 - Article
C2 - 33816397
AN - SCOPUS:85103493075
SN - 2296-2360
VL - 9
JO - Frontiers in Pediatrics
JF - Frontiers in Pediatrics
M1 - 624116
ER -