DOCK2 Deficiency in a Patient with Hyper IgM Phenotype

Alizadeh, Zahra; Mazinani, Marzieh; Shakerian, Leila; Nabavi, Mohammad; Fazlollahi, Mohammad Reza

doi:10.1007/s10875-017-0468-5

Cited by 26 publications

(27 citation statements)

References 5 publications

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“…identified five patients from five unrelated and geographically disparate families with a combined immunodeficiency because of bi‐allelic mutations in DOCK2 (OMIM 603122) . A sixth patient was reported in 2018, while several additional patients and kindreds have been presented at recent meetings of the European Society for Immunodeficiencies (ESID) or identified by the authors (unpublished data). All identified mutations are either nonsense mutations, introducing premature stop codons within the reading frame of DOCK2 , or missense mutations affecting evolutionarily conserved amino acids.…”

Section: Pids Because Of Defects In Actin Cytoskeleton Dynamicsmentioning

confidence: 99%

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Human inborn errors of the actin cytoskeleton affecting immunity: way beyond WAS and WIP

et al. 2019

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Section: Pids Because Of Defects In Actin Cytoskeleton Dynamicsmentioning

confidence: 99%

“…Antigen‐specific antibody production is often deficient. Interestingly, only a single patient has been reported to have elevated levels of serum IgE …”

Section: Pids Because Of Defects In Actin Cytoskeleton Dynamicsmentioning

confidence: 99%

Human inborn errors of the actin cytoskeleton affecting immunity: way beyond WAS and WIP

et al. 2019

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“…Patients with DOCK2 deficiency have recurrent infections and increased susceptibility to CMV. They have reduced antibody responses to T‐dependent antigens . In addition, DOCK2 deficient patients have T cell lymphopenia with low TRECs and a decrease in naive cells, along with impaired in vitro T cell proliferation to mitogens .…”

Section: Human Disease Caused By Regulators Of the Actin Cytoskeletonmentioning

confidence: 99%

“…They have reduced antibody responses to T-dependent antigens. 174,175 In addition, DOCK2 deficient patients have T cell lymphopenia with low TRECs and a decrease in naive cells, along with impaired in vitro T cell proliferation to mitogens. 175 DOCK2 expression is important for RAC activation and cell migration in response to chemoattractants.…”

Section: Dock2mentioning

confidence: 99%

Primary immunodeficiencies caused by mutations in actin regulatory proteins

Janssen

2018

Immunological Reviews

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Summary The identification of patients with monogenic gene defects have illuminated the function of different proteins in the immune system, including proteins that regulate the actin cytoskeleton. Many of these actin regulatory proteins are exclusively expressed in leukocytes and regulate the formation and branching of actin filaments. Their absence or abnormal function leads to defects in immune cell shape, cellular projections, migration, and signaling. Through the study of patients’ mutations and generation of mouse models that recapitulate the patients’ phenotypes, our laboratory and others have gained a better understanding of the role these proteins play in cell biology and the underlying pathogenesis of immunodeficiencies and immune dysregulatory syndromes.

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“…Clinical phenotype, pathogenesis, and prognosis related to the treatment of this specific form are well characterized. Elevated IgM levels were also reported in other well-defined immunodeficiencies, such as nuclear factor κB (NF-κB) essential modulator (NEMO), recombination-activating gene (RAG) 2, lipopolysaccharide-responsive beige-like anchor (LRBA), ataxia telangiectasia mutated (ATM), ARTEMIS, and dedicator of cytokinesis (DOCK) 2 deficiency [3,[18][19][20][21][22][23]. Most of these conditions are characterized by increased susceptibility to malignancies and infections.…”

Section: Introductionmentioning

confidence: 99%

Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels

Gallo

Cirillo

Prencipe

et al. 2020

JCM

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Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B-and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies.

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DOCK2 Deficiency in a Patient with Hyper IgM Phenotype

Cited by 26 publications

References 5 publications

Human inborn errors of the actin cytoskeleton affecting immunity: way beyond WAS and WIP

Human inborn errors of the actin cytoskeleton affecting immunity: way beyond WAS and WIP

Primary immunodeficiencies caused by mutations in actin regulatory proteins

Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels

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