DOCK8 Deficiency Presenting as an IPEX-Like Disorder

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dc.contributor.authorAlroqi, Fayhan J.
dc.contributor.authorCharbonnier, Louis-Marie
dc.contributor.authorKeles, Sevgi
dc.contributor.authorGhandour, Fatima
dc.contributor.authorMouawad, Pierre
dc.contributor.authorSabouneh, Rami
dc.contributor.authorMohammed, Reem
dc.date.accessioned2024-02-23T13:56:14Z
dc.date.available2024-02-23T13:56:14Z
dc.date.issued2017
dc.departmentNEÜen_US
dc.description.abstractThe dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (T-reg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C > T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G -> A). T-reg cell function was severely compromised by both DOCK8 mutations. DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.en_US
dc.description.sponsorshipNational Institutes of Health [R01AI085090, 4R01AI100315]; Scientific and Technological Research Council of Turkey [1059B191300622]en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health R01AI085090 to Talal A. Chatila and 4R01AI100315 to Raif S. Geha and by a grant from the Scientific and Technological Research Council of Turkey (1059B191300622) to Sevgi Keles.en_US
dc.identifier.doi10.1007/s10875-017-0451-1
dc.identifier.endpage819en_US
dc.identifier.issn0271-9142
dc.identifier.issn1573-2592
dc.identifier.issue8en_US
dc.identifier.pmid29058101en_US
dc.identifier.scopus2-s2.0-85031905581en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage811en_US
dc.identifier.urihttps://doi.org/10.1007/s10875-017-0451-1
dc.identifier.urihttps://hdl.handle.net/20.500.12452/11142
dc.identifier.volume37en_US
dc.identifier.wosWOS:000414207800011en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringer/Plenum Publishersen_US
dc.relation.ispartofJournal Of Clinical Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCombined Immunodeficiencyen_US
dc.subjectDock8en_US
dc.subjectFoxp3en_US
dc.subjectImmune Dysregulationen_US
dc.subjectIpexen_US
dc.subjectIpex-Likeen_US
dc.subjectRegulatory T Cellsen_US
dc.subjectT-Regen_US
dc.titleDOCK8 Deficiency Presenting as an IPEX-Like Disorderen_US
dc.typeArticleen_US

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