Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry

Jamee, Mahnaz; Azizi, Gholamreza; Barış, Safa; Karakoç-Aydıner, Elif; Özen, Ahmet; Kılıç, Sara Şebnem; Kose, Hulya; Chavoshzadeh, Zahra; Mahdaviani, Seyed Alireza; Momen, Tooba; Shamsian, Bibi Shahin; Fallahi, Mazdak; Sharafian, Samin; Gülez, Nesrin; Aygun, Ayse; Karaca, Neslihan Edeer; Kütükçüler, Necil; Sukait, Nashat Al; Farsi, Tariq Al; Al‐Tamemi, Salem; Khalifa, Nisreen; Shereen, Reda; El‐Ghoneimy, Dalia; El-Owaidy, Rasha; Radwan, Nesrine; Alzyoud, Raed; Barbouche, Mohamed‐Ridha; Ben‐Mustapha, Imen; Mekki, Najla; Rais, Afef; Boukari, Rachida; Belbouab, Reda; Djenouhat, Kamel; Tahiat, Azzeddine; Touri, Souad; ElGhazali, Gehad; Al‐Hammadi, Suleiman; Shendi, Hiba; Alkuwaiti, Amna; Belaid, Brahim; Djidjik, Réda; Artaç, Hasibe; Adeli, Mehdi; Sobh, Ali; Elnagdy, Marwa H.; Bahgat, Sara A.; Nasrullayeva, Gulnara; Chou, Janet; Rezaei, Nima; Al‐Herz, Waleed; Geha, Raif S.; Abolhassani, Hassan; Rasouli, Seyed Erfan; Esmaeili, Marzie; Yazdani, Reza; Delavari, Samaneh; Tavakol, Marzieh; Sadri, Homa; Karimi, Abdollah; Shiari, Reza; Alavi, Samin; Babaie, Delara; Eshghi, Peyman; Armin, Shahnaz; Vosughimotlagh, Ahmad; Eltan, Sevgi Bilgiç; Babayeva, Royala; Sefer, Asena Pınar; Kolukisa, Burcu; Gungoren, Ezgi Yalcin; Altunbas, Melek Yorgun; Mammadova, Vafa

doi:10.1016/j.clim.2022.109131

Cited by 14 publications

(4 citation statements)

References 40 publications

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“…According to the relatively high rate of consanguine marriage in Iran, more patients with SCID phenotype are expected to be identified, in a study by Aghamohammadi et al in 2021, 17,120 patients with IEIs from 22 countries in the Middle East and North Africa (MENA) were identified and 60.5% of cases were born in the consanguineous family [ 15 ]. The high prevalence of consanguineous marriage 20–50% in MENA countries can explain a large number of patients with IEIs in these countries [ 15 , 19 , 20 ]. Jamee et al estimated the rate of consaguinity mariage about 76% in MENA countries [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…The high prevalence of consanguineous marriage 20–50% in MENA countries can explain a large number of patients with IEIs in these countries [ 15 , 19 , 20 ]. Jamee et al estimated the rate of consaguinity mariage about 76% in MENA countries [ 20 ]. but due to the lack of proper screening programs, a notable proportion of patients die before confirmed diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene

Ghadimi

Jamee

Abolhassani

et al. 2023

Allergy Asthma Clin Immunol

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Background DCLRE1C gene mutation leads to Artemis deficiency, a severe form of combined immunodeficiency (SCID). Impaired DNA repair and block in early adaptive immunity maturation results in T-B-NK+ immunodeficiency associated with radiosensitivity. Recurrent infections early in life are the main characteristic of Artemis patients. Method Among 5373 registered patients, 9 Iranian patients (33.3% female) with confirmed DCLRE1C mutation were identified since 1999–2022. The demographic, clinical, immunological and genetic features were collected through retrospective investigation of medical records and using next generation sequencing. Results Seven patients were born in a consanguineous family (77.8%). The median age of onset was 6.0 (5.0–17.0) months. Severe combined immunodeficiency (SCID) was clinically detected at a median (IQR) age of 7.0 (6.0–20.5) months, following a median diagnostic delay of 2.0 (1.0–3.5) months The most typical first presentation was pneumonia (44.4%) and otitis media (3.33%), followed by BCG lymphadenitis (22.2%) and gastroenteritis (11.1%). The most prevalent manifestations were respiratory tract infections (including otitis media) (66.6%) and chronic diarrhea (66.6%). In addition, juvenile idiopathic arthritis (P5) and celiac disease and idiopathic thrombocytopenic purpura (P9) as autoimmune disorders were reported in 2 patients. All patients had reduced B CD19+ and CD4+ cell counts. IgA deficiency occurred in 77.8% of individuals. Conclusion Recurrent infections particulary respiratory tract infection and chronic diarrhea during the first months of life in patients born to consanguineous parents should raise the suspicion for inborn errors of immunity, even in the presence of normal growth and development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene

Ghadimi

Jamee

Abolhassani

et al. 2023

Allergy Asthma Clin Immunol

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“…The MENA registry encompasses 17,120 IEI patients from 22 countries, including 1040 individuals from Algeria alone [137]. 5871 of these patients were genetically evaluated using an approach somewhat different from ours [138] -those with highly specific, "classical" phenotypes were triaged to focused sequencing before WES, while the rest received upfront WES. Using a similar variant classification framework, this engendered an overall diagnostic yield of 83% with the majority (65.2%) of patients found to harbor recessive defects.…”

Section: Many Of Our Index Patients Did Not Present With the Most 'Ca...mentioning

confidence: 99%

A Next Generation Sequencing (NGS)-based approach to diagnosing Algerian patients with suspected Inborn Errors of Immunity (IEIs)

Peng

Al-Ddafari²,

Caballero-Oteyza³

et al. 2023

Preprint

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The advent of next-generation sequencing (NGS) technologies has greatly expanded our understanding of both the clinical spectra and genetic landscape of inborn errors of immunity (IEIs). As history has shown and recent large-scale studies of monogenic risk for severe COVID have confirmed, endogamous populations may be enriched for unique, ancestry-specific disease-causing variants as a consequence of geography and/or culture. From a diagnostic perspective, this consideration may significantly impact molecular testing and analysis strategies. Herein, we report on the diagnostic yield of a 2-step NGS-based testing approach beginning with targeted gene panels (TGPs) and reflexing to whole exome sequencing (WES) if negative for Northwest Algerian patients with suspected IEIs. A total of fourteen families were screened using TGPs tailored to their IEI subtypes of common variable immunodeficiency (CVID), inflammatory bowel disease (IBD) or chronic mucocutaneous candidiasis (CMC)-hyperIgE syndrome (HIES), resulting in a total of four definitive or highly likely molecular diagnoses (29% yield). Subsequent application of WES to eight of the ten remaining unsolved cases yielded an additional four diagnoses, giving a 57% overall yield. At least two additional individuals were found to harbor suggestive candidate variants on exome warranting further investigation, while others carried candidate variants or known risk alleles likely contributing to their clinical findings. Only in one patient’s case did we fail to identify any viable potential candidates. By achieving diagnostic yields comparable to those currently quoted for application of short-read NGS to IEI detection, our study demonstrates the viability of a 2-step NGS-based testing strategy in a selected endogamous population. Data from our localized cohort also showed some similarities and differences from NGS studies performed on larger regional IEI cohorts. Finally, our results also highlight many short-comings currently inherent to the application of genomics for clinical IEI diagnostics. Not only does the global community need to address ongoing inequities in representation, access, and infrastructure, but the ability to obtain precise and detailed clinical data remains paramount for achieving diagnostic certainty in the face of complex genotype-phenotype relationships.

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“…The prevalence rate is 0.68 per 100,000 population in Egypt (2). Another 343 patients with monogenic diseases of immune dysregulation were registered in the same region where Egypt constituted 5% of patients (3). Severe combined immunodeficiency (SCID) is a very severe form of PID, and early diagnosis can be lifesaving (4).…”

Section: Introductionmentioning

confidence: 99%

Immunological and molecular study in children with combined immunodeficiency

Kholoussi¹,

Ramadan²,

Kholoussi³

et al. 2024

Eur Ann Allergy Clin Immunol

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Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry

Cited by 14 publications

References 40 publications

Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene

Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene

A Next Generation Sequencing (NGS)-based approach to diagnosing Algerian patients with suspected Inborn Errors of Immunity (IEIs)

Immunological and molecular study in children with combined immunodeficiency

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