Evidence map›Paper›PMID 39437980›Full record

ArticleClinical immunology (Orlando, Fla.)2024

DOCK8 deficiency due to a deep intronic variant in two kindreds with hyper-IgE syndrome.

Fatma Betul Oktelik, Muyun Wang, Sevgi Keles, Hatice Eke Gungor, Murat Cansever, Salim Can, Elif Karakoc-Aydiner, Safa Baris, Klaus Schmitz-Abe, Mehdi Benamar and 1 more

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In one paragraph

Article in Clinical immunology (Orlando, Fla.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Fatma Betul OktelikDivision of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Immunology, Aziz Sancar Institute of Experimental Medicine (Aziz Sancar DETAE), Istanbul University, Istanbul, Turkiye; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Muyun WangDivision of Immunology, Boston Children's Hospital, Boston, MA, USA.
Sevgi KelesNecmettin Erbakan University, Medical Faculty, Department of Pediatric Allergy and Immunology, Konya, Turkiye.
Hatice Eke GungorUniversity of Health Sciences, Kayseri City Hospital, Department of Pediatric Allergy and Immunology, Kayseri, Turkiye.
Murat CanseverUniversity of Health Sciences, Kayseri City Hospital, Department of Pediatric Allergy and Immunology, Kayseri, Turkiye.
Salim CanMarmara University, School of Medicine, Division of Pediatric Allergy and Immunology, Istanbul, Turkiye; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkiye; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkiye.
Elif Karakoc-AydinerMarmara University, School of Medicine, Division of Pediatric Allergy and Immunology, Istanbul, Turkiye; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkiye; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkiye.
Safa BarisMarmara University, School of Medicine, Division of Pediatric Allergy and Immunology, Istanbul, Turkiye; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkiye; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkiye.
Klaus Schmitz-AbeDivision of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine and Jackson Health System, Miami, FL, USA.
Mehdi BenamarDivision of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Talal A ChatilaDivision of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: talal.chatila@childrens.harvard.edu.

Funding

Mechanisms of Combined Immunodeficiency due to DOCK8 DeficiencyR01AI128976 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI CHATILA, TALAL AMINE · 2018 to 2021
$1.4M
NIAID NIH HHS R01 AI128976
6 · The paper itself

Abstract

Dedicator of cytokinesis 8 (DOCK8) deficiency underlies the majority of cases of patients with autosomal recessive form of the hyper-immunoglobulin E syndrome (HIES). Most DOCK8 mutations involve deletions and splice junction mutations that abrogate protein expression. However, a few patients whose presentation is reminiscent of DOCK8 deficiency have no identifiable mutations. Using Whole Exome Sequencing (WES), we identified a deep intronic homozygous DOCK8 variant located in intron 36 (c.4626 + 76 A > G) in two unrelated patients with features of HIES that resulted in an in-frame 75 base pair intronic sequence insertion in DOCK8 cDNA, resulting in a premature stop codon (p.S1542ins6Ter). This variant resulted in variable decrease in DOCK8 expression that was associated with impaired T cell receptor-triggered actin polymerization, decreased IL-6-induced STAT3 phosphorylation, reduced expression of the Th17 cell markers CCR6 and IL-17, and higher frequencies of GATA3

Indexed as

Guanine Nucleotide Exchange FactorsIntronsJob SyndromePedigreeChildChild, PreschoolExome SequencingFemaleHumansMaleMutationSTAT3 Transcription FactorDOCK8 protein, humanGuanine Nucleotide Exchange FactorsSTAT3 Transcription FactorDOCK8Hyper-immunoglobulin E syndrome (HIES)Inborn errors of immunityIntronic mutationWhole exome sequencing (WES)

Identifiers

PMID39437980
PMCPMC11531991

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.