Publication:
The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency

dc.contributor.authorEngelhardt, Karin R.
dc.contributor.authorGertz, Michael E.
dc.contributor.authorKeleş, Sevgi
dc.contributor.authorSchaeffer, Alejandro A.
dc.contributor.authorSigmund, Elena C.
dc.contributor.authorGlocker, Cristina
dc.contributor.authorSaghafi, Shiva
dc.contributor.authorPourpak, Zahra
dc.contributor.authorCeja, Ruben
dc.contributor.authorSassi, Atfa
dc.contributor.authorGraham, Laura E.
dc.contributor.authorMassaad, Michel J.
dc.contributor.authorMellouli, Fethi
dc.contributor.authorBen-Mustapha, Imen
dc.contributor.authorKhemiri, Monia
dc.contributor.authorKılıç, Sara Şebnem
dc.contributor.authorEtzioni, Amos
dc.contributor.authorFreeman, Alexandra F.
dc.contributor.authorThiel, Jens
dc.contributor.authorSchulze, Ilka
dc.contributor.authorAl-Herz, Waleed
dc.contributor.authorMetin, Ayse
dc.contributor.authorSanal, Oezden
dc.contributor.authorTezcan, Ilhan
dc.contributor.authorYeganeh, Mehdi
dc.contributor.authorNiehues, Tim
dc.contributor.authorDueckers, Gregor
dc.contributor.authorWeinspach, Sebastian
dc.contributor.authorPatiroglu, Turkan
dc.contributor.authorÜnal, Ekrem
dc.contributor.authorDasouki, Majed
dc.contributor.authorYılmaz, Mustafa
dc.contributor.authorGenel, Ferah
dc.contributor.authorAytekin, Caner
dc.contributor.authorKütükçüler, Necil
dc.contributor.authorSomer, Ayper
dc.contributor.authorKılıç, Mehmet
dc.contributor.authorReisli, Ismail
dc.contributor.authorCamcioğlu, Yıldız
dc.contributor.authorGennery, Andrew R.
dc.contributor.authorCant, Andrew J.
dc.contributor.authorJones, Alison
dc.contributor.authorGaspar, Bobby H.
dc.contributor.authorArkwright, Peter D.
dc.contributor.authorPietrogrande, Maria C.
dc.contributor.authorBaz, Zeina
dc.contributor.authorAl-Tamemi, Salem
dc.contributor.authorLougaris, Vassilios
dc.contributor.authorLefranc, Gerard
dc.contributor.authorMegarbane, Andre
dc.contributor.authorBoutros, Jeannette
dc.contributor.authorGalal, Nermeen
dc.contributor.authorBejaoui, Mohamed
dc.contributor.authorBarbouche, Mohamed-Ridha
dc.contributor.authorGeha, Raif S.
dc.contributor.authorChatila, Talal A.
dc.contributor.authorGrimbacher, Bodo
dc.contributor.buuauthorKILIÇ GÜLTEKİN, SARA ŞEBNEM
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.
dc.contributor.researcheridAAH-1658-2021
dc.date.accessioned2024-08-13T07:07:24Z
dc.date.available2024-08-13T07:07:24Z
dc.date.issued2015-08-01
dc.description.abstractBackground: Mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency (CID) also classified as autosomal recessive (AR) hyper-IgE syndrome (HIES). Recognizing patients with CID/HIES is of clinical importance because of the difference in prognosis and management.Objectives: We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings.Methods: Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations.Results: DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/mu L (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4(+) and CD8(+) T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations.Conclusions: DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.
dc.description.sponsorshipFederal Ministry of Education & Research (BMBF) BMBF 01EO1303
dc.description.sponsorshipEuropean Community Health-F5-2008-223292
dc.description.sponsorshipEuropean Union (EU) MEXT-CT-2006-042316-PIAID
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA 5R01AI065617 / 1R21AI087627
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Library of Medicine (NLM)
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Allergy & Infectious Diseases (NIAID)
dc.identifier.doi10.1016/j.jaci.2014.12.1945
dc.identifier.endpage412
dc.identifier.issn0091-6749
dc.identifier.issue2
dc.identifier.startpage402
dc.identifier.urihttps://doi.org/10.1016/j.jaci.2014.12.1945
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0091674915000718
dc.identifier.urihttps://hdl.handle.net/11452/43960
dc.identifier.volume136
dc.identifier.wos000359004900022
dc.indexed.wosWOS.SCI
dc.language.isoen
dc.publisherMosby-Elsevier
dc.relation.journalJournal of Allergy and Clinical Immunology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.relation.tubitak1059B191300622
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHyper-ige syndrome
dc.subjectBone-marrow-transplantation
dc.subjectStem-cell transplantation
dc.subjectDock8 deficiency
dc.subjectMutations
dc.subjectImmunodeficiency
dc.subjectStat3
dc.subjectGlycosylation
dc.subjectDisorder
dc.subjectSurvival
dc.subjectPrimary combined immunodeficiency
dc.subjectHyper-ige syndrome
dc.subjectAutosomal recessive hyper-ige syndrome
dc.subjectDedicator of cytokinesis 8
dc.subjectSignal transducer and activator of transcription 3
dc.subjectMolluscum contagiosum
dc.subjectAllergy
dc.subjectImmunology
dc.titleThe extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency
dc.typeArticle
dspace.entity.typePublication
relation.isAuthorOfPublicationcb4f5525-5861-44f7-8234-fc2b376a934d
relation.isAuthorOfPublication.latestForDiscoverycb4f5525-5861-44f7-8234-fc2b376a934d

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Kilic_vd_2015_2.pdf
Size:
1.43 MB
Format:
Adobe Portable Document Format

Collections