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Synergistic defects of novo FAS and homozygous UNC13D leading to autoimmune lymphoproliferative syndrome-like disease: A 10-year-old Chinese boy case report
- Source :
- Gene. 672:45-49
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Autoimmune lymphoproliferative syndrome (ALPS) usually presents in childhood with fever, nonmalignant splenomegaly and lymphadenopathy along with hemocytopenia. This case report describes a 10-year-old boy presenting with signs of autoimmune disease, splenomegaly, hepatomegaly and resistant hemocytopenia. Sirolimus controlled the relapsed thrombocytopenia after splenectomy. Sequencing of the FAS gene identified two spontaneous heterozygous mutations (c.234 T > G, p.D78E) (c.236dupA, p.P80Tfs*26). The boy's homozygous missense variation (c.2588G > A, p.G863D) (rs140184929) in UNC13D gene had been identified as being related to familial hemophagocytic lymphohistiocytosis (FHL). TCRαβ + CD4/CD8 double-negative T cells (markers of ALPS) were not significantly increased from the outset. Elevated cytokines, such as interferon (IFN)-γ, interleukin (IL)-6 and tumor necrosis factor α decreased to normal levels after splenectomy whereas IL-10 remained high. Immunological analysis of the patient revealed a marked depletion of forkhead-box P3+ expressing regulatory T cells (Treg) and Th17 cells. The obtained data demonstrate that mutations to FAS and UNC13D which result in overwhelming T-cell and macrophage activation, one associated with inhibited Treg cell development and a severe ALPS-like symptom. Therefore, we propose that variations of UND13D may be a risk factor of ALPS development.
- Subjects :
- Male
0301 basic medicine
China
medicine.medical_treatment
DNA Mutational Analysis
Splenectomy
Biology
03 medical and health sciences
0302 clinical medicine
Genetics
medicine
Humans
UNC13D
fas Receptor
Child
Genetic Association Studies
Autoimmune disease
Base Sequence
Autoimmune Lymphoproliferative Syndrome
Membrane Proteins
Interleukin
Epistasis, Genetic
General Medicine
Familial Hemophagocytic Lymphohistiocytosis
medicine.disease
Fas receptor
030104 developmental biology
Autoimmune lymphoproliferative syndrome
Immunology
CD8
030215 immunology
Subjects
Details
- ISSN :
- 03781119
- Volume :
- 672
- Database :
- OpenAIRE
- Journal :
- Gene
- Accession number :
- edsair.doi.dedup.....1e9884c0949a88a8f605920f19cc3bad