Early Diagnosis in Dedicator of Cytokinesis 8 (DOCK8) Deficiency

Chang, Deidre R.; Toh, Jennifer; Vos, Gabriele de; Гаврилова, Т. В.

doi:10.1016/j.jpeds.2016.08.081

Cited by 7 publications

(7 citation statements)

References 19 publications

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“…The majority of patients with DOCK8 deficiency are of Turkish and Arabic descent, populations in which consanguinity rates are high [50–52]. However, the condition has been identified in other populations throughout the world, including North and South America, Europe, and China [8,19,38]. …”

Section: Epidemiologymentioning

confidence: 99%

“…The high frequency of deletions may be attributed to the repetitive genomic sequences around and within DOCK8 , leading to abnormal recombinations [7,8]. Other mutations described in DOCK8-deficient patients include nonsense and splice site mutations, as well as single and 2 base pair insertions [6,37,38,43]. Missense mutations are rare, with only two patients reported to date (discussed below) [7,47].…”

Section: Genetics Of Dock8 Deficiencymentioning

confidence: 99%

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DOCK8 deficiency: Insights into pathophysiology, clinical features and management

Biggs

Keleş

Chatila

2017

Clinical Immunology

144

119

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Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer. It is caused by loss of function mutations in DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes that regulates the actin cytoskeleton. Additional roles of DOCK8 have also emerged, including regulating MyD88-dependent Toll-like receptor signaling and the activation of the transcription factor STAT3. DOCK8 deficiency impairs immune cell migration, function and survival, and it impacts both innate and adaptive immune responses. Clinically, DOCK8 deficiency is characterized by allergic inflammation as well as susceptibility towards infections, autoimmunity and malignancy. This review details the pathophysiology, clinical features and management of DOCK8 deficiency. It also surveys the recently discovered combined immunodeficiency due to DOCK2 deficiency, highlighting in the process the emerging spectrum of PIDs resulting from DOCK protein family abnormalities.

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Section: Epidemiologymentioning

confidence: 99%

Section: Genetics Of Dock8 Deficiencymentioning

confidence: 99%

DOCK8 deficiency: Insights into pathophysiology, clinical features and management

Biggs

Keleş

Chatila

2017

Clinical Immunology

144

119

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“…indicated by a severe course of an actually benign poxvirus infection, such as molluscum contagiosum: For example, eczema molluscatum is typical of congenital dedicator of cytokinesis 8 (DOCK8) deficiency, a combined immunodeficiency syndrome. 280,281 Pre-existing immunodeficiency is a relevant risk factor for severe disease.…”

Section: Immunosuppressionmentioning

confidence: 99%

Poxvirus infections in dermatology – the neglected, the notable, and the notorious

Obermeier,

Buder,

Hillen

2023

J Deutsche Derma Gesell

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SummaryThe family Poxviridae currently comprises 22 genera that infect vertebrates. Of these, members of the Ortho‐, Para‐, Mollusci‐ and Yatapoxvirus genera have been associated with human diseases of high clinical relevance in dermatology. Historically, smallpox had been a notorious health threat until it was declared eradicated by the World Health Organization in 1979. Today, dermatologists are confronted with a variety of poxviral infections, such as farmyard pox, which occurs as a zoonotic infection after contact with animals. In the tropics, tanapox or vaccinia may be in the differential diagnosis as neglected tropical dermatoses. Molluscum contagiosum virus infection accounts for significant disease burden worldwide and is classified as a sexually transmitted infection in certain scenarios. Recently, mpox (monkeypox) has emerged as a public health emergency of international concern, requiring rapid recognition and appropriate management by dermatologists and infectious disease specialists. Advances and new insights into the epidemiology, diagnosis, clinical manifestations and complications, treatment, and prevention of poxviral infections require a high level of expertise and interdisciplinary skills from healthcare professionals linking virology, infectious diseases, and dermatology. This CME article provides a systematic overview and update to assist the practicing dermatologist in the identification, differential diagnosis, and management of poxviral infections.

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“…2,[5][6][7] However, this primary immunodeficiency has also been observed in additional populations around the world, including the Americas, Asia, and Europe. 5,8,9 DOCK8 deficiency generally manifests during childhood, from the first month to early years of life. 2,10 Because the DOCK8 gene regulates T and B cell number and function, pediatric patients with DOCK8 deficiency typically present with multiple abnormalities of the immune system, resulting in increased susceptibility to viral, bacterial, and fungal infections.…”

mentioning

confidence: 99%

“…To date, ~230 cases have been described, predominantly in countries with a high incidence of consanguinity 2,5–7. However, this primary immunodeficiency has also been observed in additional populations around the world, including the Americas, Asia, and Europe 5,8,9…”

mentioning

confidence: 99%

Thoracic Multidetector Computed Tomography Findings of Dedicator of Cytokinesis 8 Deficiency in Children

Lee¹,

Vargas²,

Gaffin

et al. 2021

Journal of Thoracic Imaging

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Purpose: To investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of dedicator of cytokinesis 8 (DOCK8) deficiency, a rare autosomal recessive form of hyperimmunoglobulin E syndrome, in children.Materials and Methods: All pediatric patients (age 18 y and below) with a known diagnosis of DOCK8 deficiency based on genetic testing who underwent thoracic MDCT studies from November 2004 to November 2020 were included. Two pediatric radiologists independently evaluated MDCT studies for the presence of thoracic abnormalities in the lung [ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, and bronchiectasis], pleura (pleural effusion and pneumothorax), and mediastinum (lymphadenopathy). When a lung abnormality was present, laterality, distribution (upper, middle, and lower lung zone), and extent were also evaluated. When a pleural abnormality was identified, laterality and size of the abnormality were also assessed. When mediastinal lymphadenopathy was present, its location and size were also evaluated. Interobserver agreement between two independent reviewers was evaluated with κ statistics.Results: In all, 17 thoracic MDCT studies from 17 individual pediatric patients [5 males (29%) and 12 females (71%); mean age: 7.4 y; SD: 3.7; range: 1 to 13 y] comprised the final study population. Among 17 thoracic MDCT studies, 11 studies (65%) were performed with intravenous contrast (IV) and the remaining 6 MDCT studies (35%) were obtained without IV contrast. Bilateral bronchiectasis (11/17; 65%) with a middle lung zone predominance (8/11; 73%) was the most frequently detected lung abnormality, followed by GGO in 9/17 patients (53%). Among 11 contrastenhanced MDCT studies, the majority (9 patients, 82%) had mediastinal lymphadenopathy. There was excellent interobserver κ agreement between 2 independent reviewers for detecting abnormalities on thoracic MDCT studies (κ > 0.90). Conclusion:Children with DOCK8 deficiency have characteristic thoracic MDCT findings, including bilateral bronchiectasis with a middle lung zone predominance, GGO, and mediastinal lymphadenopathy. When these characteristic thoracic MDCT findings are detected, although rare, DOCK8 deficiency should be considered as a possible underlying diagnosis in the pediatric population.

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Early Diagnosis in Dedicator of Cytokinesis 8 (DOCK8) Deficiency

Cited by 7 publications

References 19 publications

DOCK8 deficiency: Insights into pathophysiology, clinical features and management

DOCK8 deficiency: Insights into pathophysiology, clinical features and management

Poxvirus infections in dermatology – the neglected, the notable, and the notorious

Thoracic Multidetector Computed Tomography Findings of Dedicator of Cytokinesis 8 Deficiency in Children

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