Correlation between flow cytometry and molecular findings in autosomal recessive chronic granulomatous disease: A cohort study from Oman

Al-Riyami, Arwa Z.; Al-Zadjali, Shoaib; Al-Mamari, Sahimah; Al‐Said, B.; Al‐Qassabi, J.; Al‐Tamemi, Salem

doi:10.1111/ijlh.12873

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…This report confirms our previous finding that the most common form of CGD in Jordan is the AR type (21). The high frequency of AR-CGD appears also in Tunisia, Egypt, Turkey, Iran, Oman, Saudi Arabia, and Israel because of the high rate of consanguineous marriage in these countries (16,19,23,24,(48)(49)(50)(51) and it is in contrast to the published literature from USA, Europe, South America, China, and Japan, in which X-CGD is the main genetic form (4, 5,17,[25][26][27][52][53][54]. The population in Jordan amounted from 5.3 million in 2004 to 10.2 million in 2020, and is composed of a variety of ethnic groups, the majority being Arabs.…”

Section: Discussionsupporting

confidence: 90%

“…It is also the case in Egypt and Tunisia (23,49). However, in Israel, Saudi Arabia, Libya, Oman, Iran, and India, the AR47 0 CGD form prevails (16,24,48,51,59,64,65). However, in Turkey about 30-40% of the CGD patients have X-CGD, but AR47 0 CGD represents about 30-50% of AR-CGD too (19,75,76).…”

Section: Discussionmentioning

confidence: 95%

“…It is situated in the first SH3 (SRC homology 3) domain of p47 phox involved in the binding with p22 phox during the NADPH oxidase assembly for activation (67). It is a quite worldwide rare mutation except in Israel (16,46) and it is also the predominant NCF1 mutation found in AR47 0 CGD patients in Oman (48). In Israel population, the Trp193 * mutation is predominantly found in Kavkazi Jewish patients.…”

Section: Discussionmentioning

confidence: 99%

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Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

et al. 2021

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Chronic granulomatous Disease (CGD) is a rare innate immunodeficiency disorder caused by mutations in one of the six genes (CYBA, CYBB, NCF1, NCF2, NCF4, and CYBC1/EROS) encoding the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH)—oxidase complex in phagocytes. In the Western population, the most prevalent form of CGD (about two-thirds of all cases) is the X-linked form (X-CGD) caused by mutations in CYBB. The autosomal recessive forms (AR-CGD), due to mutations in the other genes, collectively account for the remaining one-third of CGD cases. We investigated the clinical and molecular features of 22 Jordanian, 7 Libyan, and 2 Iraqi CGD patients from 21 different families. In addition, 11 sibling patients from these families were suspected to have been died from CGD as suggested by their familial and clinical history. All patients except 9 were children of consanguineous parents. Most of the patients suffered from AR-CGD, with mutations in CYBA, NCF1, and NCF2, encoding p22phox, p47phox, and p67phox proteins, respectively. AR-CGD was the most frequent form, in Jordan probably because consanguineous marriages are common in this country. Only one patient from non-consanguineous parents suffered from an X910 CGD subtype (0 indicates no protein expression). AR670 CGD and AR220 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR470 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

et al. 2021

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“…Notably, a high neutrophil SI detected using the DHR123 test does not indicate mild symptoms or a good prognosis for patients with variant type X-linked CGD. Although DHR has the advantages of requiring a small blood volume, short time, and convenience compared with direct superoxide detection, it has limitations in terms of molecular mechanism [ 64 ]. NADPH oxidase transfers electrons to molecular oxygen to generate O 2 − , which is dismutated to hydrogen peroxide (H 2 O 2 ).…”

Section: Discussionmentioning

confidence: 99%

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

et al. 2022

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Purpose We aimed to report the clinical and immunological characteristics of variant type X91+ chronic granulomatous disease (CGD) in a Chinese cohort. Methods The clinical manifestations and immunological phenotypes of patients with X91+ CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91phox protein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 and flow cytometry. Results Patients with X91+ CGD accounted for 8% (7/85) of all patients with CGD. The median age of onset in the seven patients with X91+ CGD was 4 months. Six patients received the BCG vaccine, and 50% (3/6) had probable BCG infections. Mycobacterium tuberculosis infection was prominent. The most common sites of infection were the lung (6/7), lymph nodes (5/7), and soft tissue (3/7). Two patients experienced recurrent oral ulcers. The stimulation index (SI) of the patients with X91+ CGD ranged widely from 1.9 to 67.3. The difference in the SI among the three groups of patients (X91+ CGD, X91− CGD, and X910 CGD) was statistically significant (P = 0.0071). The three groups showed no significant differences in onset age, diagnosis age, or severe infection frequency. CYBB mutations associated with X91+ CGD were commonly located in the second transmembrane or intracellular regions. Three novel X91+ CGD–related mutations (c.1462–2 A > T, c.1243C > T, and c.925G > A) were identified. Conclusions Variant type X91+ CGD may result in varied clinical manifestations. Moreover, the laboratory findings might indicate a moderate neutrophil SI. We should deepen our understanding of variant X91+ CGD to prevent missed diagnoses.

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“…Thus, flow cytometry helps to identify the genotype-dependent variability in the evaluation of NADPH oxidase activity. It has been observed that autosomal recessive (AR-CGD) subtypes ( CYBA, NCF1, NCF2 , and NCF4 gene defects) have slightly higher amounts of residual superoxide activity compared with the X-linked recessive (XL-CGD) subtype ( CYBB gene defect) patients (48, 54). This mainly affects the severity of the clinical progression.…”

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India

et al. 2019

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Primary immunodeficiency diseases (PID) are a clinically and immunologically heterogeneous group of disorders of immune system. Diagnosis of these disorders is often challenging and requires identification of underlying genetic defects, complemented by a comprehensive evaluation of immune system. Flow cytometry, with its advances in the last few decades, has emerged as an indispensable tool for enumeration as well as characterization of immune cells. Flow cytometric evaluation of the immune system not only provides clues to underlying genetic defects in certain PIDs and helps in functional validation of novel genetic defects, but is also useful in monitoring immune responses following specific therapies. India has witnessed significant progress in the field of flow cytometry as well as PID over last one decade. Currently, there are seven Federation of Primary Immunodeficiency Diseases (FPID) recognized centers across India, including two Indian Council of Medical research (ICMR) funded centers of excellence for diagnosis, and management of PIDs. These centers offer comprehensive care for PIDs including flow cytometry based evaluation. The key question which always remains is how one selects from the wide array of flow cytometry based tests available, and whether all these tests should be performed before or after the identification of genetic defects. This becomes crucial, especially when resources are limited and patients have to pay for the investigations. In this review, we will share some of our experiences based on evaluation of a large cohort of hemophagocytic lymphohistiocytosis, severe combined immunodeficiency, and chronic granulomatous disease, and the lessons learned for optimum use of this powerful technology for diagnosis of these disorders.

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Correlation between flow cytometry and molecular findings in autosomal recessive chronic granulomatous disease: A cohort study from Oman

Abstract: Flow cytometry is a robust test of CGD diagnosis. However, results should be interpreted with caution when predicting the underlying probable genotype, and results need to be complemented with definitive molecular studies.

Cited by 5 publications

References 34 publications

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India

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