De Novo Somatic Mosaicism of CYBB Caused by Intronic LINE-1 Element Insertion Resulting in Chronic Granulomatous Disease

Yu, Lang; Li, Wenhui; Lv, Ge; Sun, Gan; Yang, Ling; Chen, Junjie; Zhou, Lina; Yuan, Ding; Zhang, Zhiyong; Tang, Xuemei; An, Yunfei; Zhao, Xiaodong

doi:10.1007/s10875-022-01347-w

Cited by 10 publications

(2 citation statements)

References 44 publications

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“…Next, SYTOX green (2.5 μM) was added for 5 min, 30 min, or 1, 2, 3, 4, or 5 h. 0.1%Triton X-100 and KRG + solutions were used as positive and negative controls, respectively. The specific method has been described previously [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine

Sun

et al. 2023

J Clin Immunol

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The dedicator of cytokinesis 2(DOCK2) protein, an atypical guanine nucleotide exchange factor (GEFs), is a member of the DOCKA protein subfamily. DOCK2 protein deficiency is characterized by early-onset lymphopenia, recurrent infections, and lymphocyte dysfunction, which was classified as combined immune deficiency with neutrophil abnormalities as well. The only cure is hematopoietic stem cell transplantation. Here, we report two patients harboring four novel DOCK2 mutations associated with recurrent infections including live attenuated vaccine-related infections. The patient’s condition was partially alleviated by symptomatic treatment or intravenous immunoglobulin. We also confirmed defects in thymic T cell output and T cell proliferation, as well as aberrant skewing of T/B cell subset TCR-Vβ repertoires. In addition, we noted neutrophil defects, the weakening of actin polymerization, and BCR internalization under TCR/BCR activation. Finally, we found that the DOCK2 protein affected antibody affinity although with normal total serum immunoglobulin. The results reported herein expand the clinical phenotype, the pathogenic DOCK2 mutation database, and the immune characteristics of DOCK2-deficient patients. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-023-01466-y.

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Section: Methodsmentioning

confidence: 99%

Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine

Sun

et al. 2023

J Clin Immunol

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“…Respiratory burst was measured by ow cytometry using dihydrorhodamine-1,2,3 (DHR) (Sigma-Aldrich). Brie y, whole blood from the patient and his parents was incubated with DHR and stimulated with phorbol 12-myristate 13-acetate (PMA) (Sigma-Aldrich), as described previously [19]. The results are presented as a stimulation index (SI), which was calculated for gated neutrophils by estimating the ratio of the median uorescence intensity (MFI) of PMA-stimulated to that of PMA-unstimulated cells [20].…”

Section: Respiratory Burst By Neutrophilsmentioning

confidence: 99%

Novel Compound Heterozygous CYBA Mutations Causing Neonatal-Onset Chronic Granulomatous Disease

Zhang

et al. 2023

J Clin Immunol

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Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI) characterized by a defective respiratory burst by phagocytes and defective clearance of phagocytosed microorganisms; these phenomena, caused by a defect in NADPH oxidase, result in severe and life-threatening infections in affected children. The genetically heterogeneous X-linked recessive (XL-CGD) form of GCD is caused by mutations in the CYBB gene, whereas the autosomal recessive (AR-CGD) form is caused by mutations in the CYBA, NCF1, NCF2, NCF4, or CYBC1 genes. Mutations in the CYBA gene account for a small number of CGD cases; the vast majority of these patients become symptomatic in childhood, but rarely within the rst weeks of life. Here, we report a 19-day-old neonate who developed pustular rashes and invasive pulmonary aspergillosis, which was identi ed by a galactomannan (GM) assay of both bronchoalveolar lavage uid (BALF) and peripheral blood samples, and by metagenomic next-generation sequencing (mNGS) of BALF. A diagnosis of CGD was based on the respiratory burst test. Detailed assessment of neutrophil activity revealed that production of reactive oxygen species (ROS) was entirely absent. Wholeexome sequencing (WES) detected a nonsense mutation (c.7G>T). In addition, copy number variation (CNV) analysis detected a novel de novomicrodeletion of 200 kb at 16q24.2-q24.3. Thus, we have identi ed novel compound heterozygous CYBA mutations that cause neonatal AR-CGD, thereby expanding the clinical spectrum of CYBA de ciency.

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Molecular Challenges in the Diagnosis of X-Linked Chronic Granulomatous Disease: CNVs, Intronic Variants, Skewed X-Chromosome Inactivation, and Gonosomal Mosaicism

Batlle-Masó,

Rivière,

Franco-Jarava

et al. 2023

J Clin Immunol

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De Novo Somatic Mosaicism of CYBB Caused by Intronic LINE-1 Element Insertion Resulting in Chronic Granulomatous Disease

Cited by 10 publications

References 44 publications

Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine

Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine

Novel Compound Heterozygous CYBA Mutations Causing Neonatal-Onset Chronic Granulomatous Disease

Molecular Challenges in the Diagnosis of X-Linked Chronic Granulomatous Disease: CNVs, Intronic Variants, Skewed X-Chromosome Inactivation, and Gonosomal Mosaicism

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