AUTHOR=Lopez-Rivera Daniela Olivia , Castano-Jaramillo Lina Maria , Yamazaki-Nakashimada Marco Antonio , Ramirez Uribe Rosa María Nideshda , Corcuera Delgado Celso Tomás , Ignorosa-Arellano Karen R. , Medina-Torres Edgar Alejandro , Berrón Ruiz Laura , Espinosa-Padilla Sara Elva , Scheffler-Mendoza Selma C. , López-Velázquez Gabriel , Cruz-Munoz Mario Ernesto , Lugo Reyes Saul O. TITLE=Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.959733 DOI=10.3389/fimmu.2022.959733 ISSN=1664-3224 ABSTRACT=Introduction

The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals.

Objective

We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology.

Methods

After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells.

Results

We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis.

Discussion

NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.