“Clinical Aspects of Chronic Granulomatous Disease in Upper Egypt”

El‐Mokhtar, Mohamed A.; Salama, Eman H; Fahmy, Eman M.; Mohamed, Mai

doi:10.1080/08820139.2020.1713144

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…In CGD/ NCF1 patients, only one variant, p.Tyr26HisfsTer26, had been identified in all patients and in CGD/ CYBA , one variant, p.Val99ProfsTer90, had been detected in almost all patients. These two variants were also the only ones reported by another study from upper Egypt [ 19 ].…”

Section: Discussionsupporting

confidence: 52%

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

et al. 2022

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Background Inborn errors of immunity (IEI) are a group of heterogeneous disorders with geographic and ethnic diversities. Although IEI are common in Egypt, genetic diagnosis is limited due to financial restrictions. This study aims to characterize the genetic spectrum of IEI patients in Egypt and highlights the adaptation of the molecular diagnostic methods to a resource-limited setting. Methods Genetic material from 504 patients was studied, and proper diagnosis was achieved in 282 patients from 246 families. Mutational analysis was done by Sanger sequencing, next-generation sequencing (NGS) targeting customized genes panels, and whole-exome sequencing (WES) according to the patients’ phenotypes and availability of genetic testing. Results A total of 194 variants involving 72 different genes were detected with RAG1/2 genes being the most encountered followed by DOCK8, CYBA, LRBA, NCF1, and JAK3. Autosomal recessive (AR) inheritance was detected in 233/282 patients (82.6%), X-linked (XL) recessive inheritance in 32/282 patients (11.3%), and autosomal dominant (AD) inheritance in 18/282 patients (6.4%), reflecting the impact of consanguineous marriages on the prevalence of different modes of inheritance and the distribution of the various IEI disorders. Conclusion The study showed that a combination of Sanger sequencing in selected patients associated with targeted NGS or WES in other patients is an effective diagnostic strategy for IEI diagnosis in countries with limited diagnostic resources. Molecular testing can be used to validate other nonexpensive laboratory techniques that help to reach definitive diagnosis and help in genetic counseling and taking proper therapeutic decisions including stem cell transplantation or gene therapy.

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Section: Discussionsupporting

confidence: 52%

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

et al. 2022

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“…In Western countries, 65%–70% of CGD cases are X-linked ( 18 , 19 ). Conversely, in a cohort of 15 children with CGD in Egypt, the most common gene mutation was CYBA ( 10 ). The targeted gene panel used in this study does not detect the hotspot deletion in NCF1 ( 20 ), which might be the most common variant in the Middle East ( 21 ), because there is a pseudogene that gets sequenced instead of NCF1 ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…In Europe, the USA, and Latin America, the X-linked form of CGD is the most common ( 6 – 8 ). The majority of African studies on inborn errors of immunity (IEIs) are from Northern African countries including Algeria, Egypt, Libya, Morocco, Sudan, and Tunisia ( 9 , 10 ), where consanguineous marriage is highly prevalent; thus, most diseases tend to be autosomal recessive ( 9 ). Data on CGD in East Africa are lacking.…”

Section: Introductionmentioning

confidence: 99%

Genetically confirmed chronic granulomatous disease in a Kenyan child: case report

Marangu-Boore,

Kambuni,

Onyinkwa

et al. 2023

Front. Immunol.

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IntroductionWe report the first case of genetically confirmed chronic granulomatous disease (CGD) in a Kenyan child.Clinical findingsA 7-month-old male infant, the only child of non-consanguineous parents, presented with cough, fever, fast breathing, oral thrush, and axillary lymphadenopathy ipsilateral to the Calmette–Guérin bacillus scar. He had been hospitalized 5 weeks prior for severe pneumonia. Plain chest radiography showed bilateral patchy airspace opacification; chest computed tomography revealed multiple large lung nodules and left axillary lymphadenopathy. HIV ELISA was negative; tuberculin skin test was positive; lymph node biopsy macroscopically revealed caseous granulomas seen on histology; isoniazid- and rifampicin-susceptible Mycobacterium tuberculosis complex isolate was detected on the Hain test. First-line anti-tuberculous drugs were added to his empiric treatment comprising piperacillin–tazobactam, amikacin, cotrimoxazole, and fluconazole. He was discharged after 10 days based on clinical resolution.Diagnoses, interventions, and outcomeAn inborn error of immunity (IEI) was considered given the recurrent fevers and atypical lung nodules. Genetic analysis revealed a hemizygous pathogenic variant on CYBB in keeping with X-linked CGD. The child’s fevers recurred 2 weeks post-discharge but completely resolved on prophylactic itraconazole and cotrimoxazole. He underwent a successful haplo-identical hematopoietic stem cell transplantation at an experienced center in India with his father as the donor and is currently doing well on post-transplant follow-up.ConclusionGenetic testing is relatively accessible and cost-effective for the diagnosis of IEI in low-and-middle-income countries. Expert multi-disciplinary collaboration is key for successful outcomes.

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“…Intriguingly, it is most common in East Asians (Chinese, Japanese, and Koreans) [31][32][33][34][35][36][37][38]. The mutation appears much less common in large cohorts from Europe and America, or even in regions with high levels of parental consanguinity such as the Middle East or India [10,15,[42][43][44][45][46][47][48][49][50][51][52][53][54][55]. The identi ed mutations in the CYBA gene reveal its allelic heterogeneity; there is no commonly affected allele or hot spots worldwide [9].…”

Section: Discussionmentioning

confidence: 99%

Novel Compound Heterozygous CYBA Mutations Causing Neonatal-Onset

Zhang¹,

Yu²,

Li³

et al. 2023

Preprint

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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 first weeks of life. Here, we report a 19-day-old neonate who developed pustular rashes and invasive pulmonary aspergillosis, which was identified by a galactomannan (GM) assay of both bronchoalveolar lavage fluid (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. Whole-exome 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 identified novel compound heterozygous CYBA mutations that cause neonatal AR-CGD, thereby expanding the clinical spectrum of CYBA deficiency.

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“Clinical Aspects of Chronic Granulomatous Disease in Upper Egypt”

Cited by 8 publications

References 52 publications

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

Genetically confirmed chronic granulomatous disease in a Kenyan child: case report

Novel Compound Heterozygous CYBA Mutations Causing Neonatal-Onset

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