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Journal article
Novel Compound Heterozygous ZAP70 R37G A507T Mutations in Infant with Severe Immunodeficiency
Journal of clinical immunology, v 44(1), pp 27-27
01 Jan 2024
PMID: 38129328
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Zeta-chain associated protein kinase 70 kDa (ZAP70) combined immunodeficiency (CID) is an autosomal recessive severe immunodeficiency that is characterized by abnormal T-cell receptor signaling. Children with the disorder typically present during the first year of life with diarrhea, failure to thrive, and recurrent bacterial, viral, or opportunistic infections. To date, the only potential cure is hematopoietic stem cell transplant (HSCT). The majority of described mutations causing disease occur in the homozygous state, though heterozygotes are reported without a clear understanding as to how the individual mutations interact to cause disease. This case describes an infant with novel ZAP-70 deficiency mutations involving the SH2 and kinase domains cured with allogeneic HSCT utilizing a reduced-intensity conditioning regimen and graft manipulation. We then were able to further elucidate the molecular signaling alterations imparted by these mutations that lead to altered immune function. In order to examine the effect of these novel compound ZAP70 heterozygous mutations on T cells, Jurkat CD4
T cells were transfected with either wild type, or with individual ZAP70 R37G and A507T mutant constructs. Downstream TCR signaling events and protein localization results link these novel mutations to the expected immunological outcome as seen in the patient's primary cells. This study further characterizes mutations in the ZAP70 gene as combined immunodeficiency and the clinical phenotype.
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Details
- Title
- Novel Compound Heterozygous ZAP70 R37G A507T Mutations in Infant with Severe Immunodeficiency
- Creators
- Nathalia Benavides - Thomas Jefferson UniversityJason C White - Thomas Jefferson UniversityMaria L Sanmillan - Thomas Jefferson UniversityMorgan Thomas - Department of Genetics, Nemours Children's Hospital Delaware, Wilmington, USATrong Le - Department of Allergy/Immunology, Nemours Children's Hospital Delaware, Wilmington, USAEmi Caywood - Department of Pediatric Hematology/Oncology, Nemours Children's Hospital Delaware, Wilmington, USAClaudio G Giraudo - Thomas Jefferson University
- Publication Details
- Journal of clinical immunology, v 44(1), pp 27-27
- Publisher
- Springer Nature
- Grant note
- P30 CA056036 / NCI NIH HHS R01 AI123538 / NIAID NIH HHS T32 AI134646 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:001127428300004
- Scopus ID
- 2-s2.0-85180488430
- Other Identifier
- 991021960633904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Immunology