Evidence map›Paper›PMID 39384643›Full record

ArticleJournal of clinical immunology2024

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

Qi Wu, Bijun Sun, Jia Hou, Xiaoying Hui, Chenghao Wang, Wenjie Wang, Wenjing Ying, Luyao Liu, Li Zhu, Ying Wang and 9 more

Abstract readCase Reports
PubMed Publisher
In one paragraph

Article in Journal of clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. T follicular helper cells in primary immune regulatory disorders.The Journal of allergy and clinical immunology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Qi Wu *Department of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Bijun Sun *Department of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Jia HouDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Xiaoying HuiDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Chenghao WangDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Wenjie WangDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Wenjing YingDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Luyao LiuDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Li ZhuDepartment of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
Ying WangKey Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
Qifan LiDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Meiping YuDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Weitao ZhouDepartment of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.
Yao ChenDepartment of Respiratory Medicine, Children's Hospital of Fudan University, Shanghai, China.
Bingbing WuClinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China.
Jinqiao SunDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
Qinhua ZhouDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China. qinhua_zhou@fudan.edu.cn.
Feng QianMinistry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, China. fengqian@fudan.edu.cn.
Xiaochuan WangDepartment of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China. xchwang@shmu.edu.cn.

Funding

"Sailing Program" of Shanghai Science and Technology Committee 23YF1403400Shanghai Municipal Science and Technology Major Project 2023SHZDZX02, 2017SHZDZX01Shanghai Municipal Science and Technology Major Project ZD2021CY001Shanghai Municipal Technology Standards Project 23DZ2202600
6 · The paper itself

Abstract

objectiveFAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism.

methodsWhole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis.

resultsThe patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA

conclusionsWe identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.

Indexed as

Autoimmune Lymphoproliferative SyndromeExome Sequencingfas ReceptorHeterozygoteApoptosisCOVID-19FemaleGenetic Predisposition to DiseaseHEK293 CellsHumansInfant, NewbornMutationSARS-CoV-2FAS protein, humanfas ReceptorApoptosisAutoimmune Lymphoproliferation SyndromeCompound heterozygous mutationsDouble-negative T CellsFASImmunophenotyping

Identifiers

PMID39384643

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.