DOCK8 Deletions and Mutations are Associated with the Autosomal Recessive Hyper-IgE Phenotype

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dc.contributor.authorMcGhee, S. A.
dc.contributor.authorEngelhardt, K.
dc.contributor.authorWinkler, S.
dc.contributor.authorSassi, A.
dc.contributor.authorWoellner, C.
dc.contributor.authorLopez-Herrera, G.
dc.contributor.authorChen, A.
dc.contributor.authorKim, H.
dc.contributor.authorGarcia Lloret, M.
dc.contributor.authorSchulze,I.
dc.contributor.authorEhl, S.
dc.contributor.authorThiel, J.
dc.contributor.authorPfeifer, D.
dc.contributor.authorVeelken, H.
dc.contributor.authorNiehues, T.
dc.contributor.authorSiepermann, K.
dc.contributor.authorWeinspach, S.
dc.contributor.authorReisli, I.
dc.contributor.authorKeleş, S.
dc.contributor.authorGenel, F.
dc.contributor.authorKütükçüker, N.
dc.contributor.authorCamcıoğlu, Y.
dc.contributor.authorSomer, A.
dc.contributor.authorKarakoç-Aydıner, E.
dc.contributor.authorBarlan, I.
dc.date.accessioned2020-03-26T17:47:54Z
dc.date.available2020-03-26T17:47:54Z
dc.date.issued2010
dc.departmentSelçuk Üniversitesien_US
dc.description66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology -- FEB 26-MAR 02, 2010 -- New Orleans, LAen_US
dc.description.abstractRATIONALE: Many patients who have a hyper-IgE like phenotype do not have mutations in STAT3 and show an autosomal recessive pattern of inheritance. The genetic cause of the immune deficiency is unexplained. METHODS: We analyzed 27 subjects with an autosomal recessive hyperIgE syndrome phenotype by mapping arrays and sequencing. Subjects were considered to have AR-HIES if they had no skeletal findings and primarily viral infections with a HIES score > 22. We performed copy number analysis and homozygosity mapping to implicate candidate loci. RESULTS: Five subjects had homozygous or compound heterozygous subtelomeric deletions involving 9p24.3, with the minimally deleted region involving only one gene, DOCK8. Sequencing of DOCK8 in the remaining patients showed nonsense and splice site mutations as well as single exon deletions within DOCK8 in 16 patients from 9 families. Patients with DOCK8 deficiency have pneumonia, skin abscesses, severe viral infections and candidiasis. Serum IgE was markedly elevated with profound eosinophilia. T cells from patients with DOCK8 deficiency had reduced proliferation from anti-CD3 stimulation. CONCLUSIONS: Deletions and mutations in DOCK8 are associated with the autosomal recessive hyper-IgE syndrome, as was also found by Zhang, et al (NEJM 2009;361:2046-55). Though its function is unknown, DOCK8 interacts with the cytoskeleton and may alter dendritic cell function, T-cell function, or both. Breakpoints for deletions appear to be near Alu Jb sequences, suggesting the possibility of retrotransposon activity as a mechanism for deletion. Genomic copy number variants are an important, newly appreciated mechanism underlying primary immune deficiency and can provide clues for disease gene identification.en_US
dc.description.sponsorshipAmer Acad Allergy, Asthma & Immunolen_US
dc.identifier.citationMcGhee, S. A., Engelhardt, K., Winkler, S., Sassi, A., Woellner, C., Lopez-Herrera, G., Chen, A., Kim, H., Garcia Lloret, M., Schulze,I., Ehl, S., Thiel, J., Pfeifer, D., Veelken, H., Niehues, T., Siepermann, K., Weinspach, S., Reisli, I., Keleş, S., Genel, F., Kütükçüker, N., Camcıoğlu, Y., Somer, A., Karakoç-Aydıner, E., Barlan, I., (2010). DOCK8 Deletions and Mutations are Associated with the Autosomal Recessive Hyper-IgE Phenotype. Journal of Allergy and Clinical Immunology, 125(2), 356. doi: org/10.1016/j.jaci.2010.01.006
dc.identifier.doi10.1016/j.jaci.2010.01.006en_US
dc.identifier.endpageAB356en_US
dc.identifier.issn0091-6749en_US
dc.identifier.issue2en_US
dc.identifier.startpageAB356en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.jaci.2010.01.006
dc.identifier.urihttps://hdl.handle.net/20.500.12395/24789
dc.identifier.volume125en_US
dc.identifier.wosWOS:000280204100931en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.institutionauthorReisli, I.
dc.language.isoenen_US
dc.publisherMOSBY-ELSEVIERen_US
dc.relation.ispartofJournal of Allergy and Clinical Immunologyen_US
dc.relation.publicationcategoryKonferans Öğesi - Uluslararası - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.titleDOCK8 Deletions and Mutations are Associated with the Autosomal Recessive Hyper-IgE Phenotypeen_US
dc.typeConference Objecten_US

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