Functional characterization of a novel IL2RG mutation causing atypical SCID

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dc.contributor.advisor Handgretinger, Rupert (Prof. Dr.)
dc.contributor.author Gratz, Hans Peter
dc.date.accessioned 2024-07-22T09:01:05Z
dc.date.available 2024-07-22T09:01:05Z
dc.date.issued 2024-07-22
dc.identifier.uri http://hdl.handle.net/10900/155233
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1552337 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-96566
dc.description.abstract The interleukin-2 receptor common gamma chain gene (IL2RG) encodes for the common gamma chain (yc), which is a part of multiple interleukin receptors such as IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 receptor. T cell proliferation and cytokine production is induced due to its activation of Janus kinase 3 (JAK3) and signal transducer and activator of transcription 5 (STAT5) depended signaling pathway. Therefore, mutations in this gene can cause impaired cell-mediated and humoral immunity leading to severe combined immunodeficiency (SCID). From birth patients suffer from total absent or greatly reduced T and NK cells being susceptible to opportunistic pathogens, which shows in recurrent respiratory and viral infections. Usually, the infants die within the first year of life unless undergoing prompt hematopoietic stem cell transplantation or gene therapy. Lately, hypomorphic mutations in the IL2RG gene with milder phenotypes have been described. Unlike SCID, the cells of the lymphatic lineage can be detected in peripheral blood count even if they display functional impairment. This work focuses on the functional characterization of a novel c.458T>C; p.Ile153Thr IL2RG missense-mutation observed in three brothers. They were diagnosed with atypical SCID due to their milder phenotype expression. Functional characterization of the common gamma chain (γc) revealed its hypomorphic function. In addition, we detected somatic reversion predominantly in lymphoid derived subpopulations. The combination of hypomorphic IL2RG function and somatic reversion explains the atypical phenotype of the patients and serves as a model for novel gene editing tools (e.g., CRISPR/Cas9) imitating the process of natural gene therapy. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podno de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en en
dc.subject.other Somatic reversion en
dc.subject.other Interleukin-2 receptor en
dc.subject.other Atypical SCID en
dc.title Functional characterization of a novel IL2RG mutation causing atypical SCID en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2023-11-10
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE
utue.publikation.noppn yes de_DE

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