Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Yazdani, Reza; Abolhassani, Hassan; Kiaee, Fatemeh; Habibi, Sima; Azizi, Gholamreza; Tavakol, Marzieh; Chavoshzadeh, Zahra; Mahdaviani, Seyed Alireza; Momen, Tooba; Gharagozlou, Mohammad; Movahedi, Masoud; Hamidieh, Amir Ali; Behniafard, Nasrin; Nabavi, Mohammad; Bemanian, Mohammad Hassan; Arshi, Saba; Molatefi, Rasol; Sherkat, Roya; Shirkani, Afshin; Amin, Reza; Aleyasin, Soheila; Faridhosseini, Reza; Jabbari‐Azad, Farahzad; Mohammadzadeh, Iraj; Ghaffari, Javad; Shafiei, Alireza; Kalantari, Arash; Mansouri, Mahboubeh; Mesdaghi, Mehrnaz; Babaie, Delara; Ahanchian, Hamid; Khoshkhui, Maryam; Soheili, Habib; Eslamian, Mohammad Hossein; Cheraghi, Taher; Dabbaghzadeh, Abbas; Tavassoli, Mahmoud; Kalmarzi, Rasoul Nasiri; Mortazavi, Seyed Hamidreza; Kashef, Sara; Esmaeilzadeh, Hossein; Tafaroji, Javad; Khalili, Abbas; Zandieh, Fariborz; Sadeghi‐Shabestari, Mahnaz; Darougar, Sepideh; Behmanesh, Fatemeh; Akbari, Hedayat; Zandkarimi, Mohammad Reza; Abolnezhadian, Farhad; Fayezi, Abbas; Moghtaderi, Mojgan; Ahmadiafshar, Akefeh; Shakerian, Behzad; Sajedi, Vahid; Taghvaei, Behrang; Safari, Mojgan; Heidarzadeh, Marzieh; Ghalebaghi, Babak; Fathi, Seyed Mohammad; Darabi, Behzad; Bazregari, Saeed; Bazargan, Nasrin; Fallahpour, Morteza; Khayatzadeh, Alireza; Javahertrash, Naser; Bashardoust, Bahram; Zamani, Mohammadali; Mohsenzadeh, Azam; Ebrahimi, Sarehsadat; Sharafian, Samin; Vosughimotlagh, Ahmad; Tafakoridelbari, Mitra; Rahim, Maziar; Ashournia, Parisa; Razaghian, Anahita; Rezaei, Arezou; Samavat, Ashraf; Mamishi, Setareh; Khazaei, Hossein Ali; Mohammadi, Javad; Negahdari, Babak; Parvaneh, Nima; Rezaei, Nima; Lougaris, Vassilios; Giliani, Silvia; Plebani, Alessandro; Ochs, Hans D.; Hammarström, Lennart; Aghamohammadi, Asghar

doi:10.1016/j.jaip.2018.09.004

Cited by 37 publications

(26 citation statements)

References 36 publications

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“…They provided an invaluable source of information about the natural history and outcome of specific diseases and documented variabilities between different populations (15–18). They have supported research on the genetic, molecular, and physiological basis of PID (19, 20). They can be used to support clinical trials and translational research to improve quality of care, quality of life, and survival.…”

Section: Introductionmentioning

confidence: 96%

The Kuwait National Primary Immunodeficiency Registry 2004–2018

et al. 2019

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Objective: To present the report from the Kuwait National Primary Immunodeficiency Registry between 2004 and 2018. Methods: The patients were followed prospectively between January 2004 and December 2018 and their collected data included sociodemographic, diagnosis, clinical presentation, laboratory tests, and treatment. Results: A total of 314 PID patients (165 males and 149 females) were registered during the study period. Most of the patients ( n = 287, 91.4%) were Kuwaiti nationals and the prevalence among Kuwaitis was 20.27/100,000 with a cumulative incidence of 24.96/100,000 Kuwaitis. The distribution of the patients according to PID categories was as follow: immunodeficiencies affecting cellular and humoral immunity, 100 patients (31.8%); combined immunodeficiencies with associated syndromic features, 68 patients (21.7%); predominantly antibody deficiencies, 56 patients (17.8%); diseases of immune dysregulation, 47 patients (15%); congenital defects of phagocyte number or function, 20 patients (6.4%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 22 patients (7%). The mean age of the patients at onset of symptoms was 26 months while the mean age at diagnosis was 53 months and the mean delay in diagnosis was 27 months. Most of the patients ( n = 272, 86%) had onset of symptoms before the age of 5 years. Parental consanguinity rate within the registered patients was 78% and a positive family history of PID was noticed in 50% of the patients. Genetic testing was performed in 69% of the patients with an overall diagnostic yield of 90%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by an autosomal recessive pattern. Intravenous immunoglobulins and stem cell transplantation were used in 58% and 25% of the patients, respectively. There were 81 deaths (26%) among the registered patients with a mean age of death of 25 months. Conclusions: PID is not infrequent in Kuwait and the reported prevalence is the highest in the literature with increased proportion of more severe forms. Collaborative efforts including introduction of newborn screening should be implemented to diagnose such cases earlier and improve the quality of life and prevent premature deaths.

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Section: Introductionmentioning

confidence: 96%

The Kuwait National Primary Immunodeficiency Registry 2004–2018

et al. 2019

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“…Immunoglobulin μ heavy chain (IGHM) deficiency is associated with more severe clinical manifestation compared to XLA ( 16 , 17 , 19 ). Like in XLA, neutropenia may be seen in 30% of these patients ( 16 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Update on Infections in Primary Antibody Deficiencies

Demirdağ

Gupta

2021

Front. Immunol.

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Bacterial respiratory tract infections are the hallmark of primary antibody deficiencies (PADs). Because they are also among the most common infections in healthy individuals, PADs are usually overlooked in these patients. Careful evaluation of the history, including frequency, chronicity, and presence of other infections, would help suspect PADs. This review will focus on infections in relatively common PADs, discussing diagnostic challenges, and some management strategies to prevent infections.

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“…In this manuscript we present genetic data collected from 184 out of 264 patients who were registered in KNPIDR from January 2004 to December 2017. To the best of our knowledge, this is one of the largest molecular studies of PID patients from a highly consanguineous population along with other studies from the region (24–27). The most represented groups in this series include combined T and B cell immunodeficiencies (157/264) (60%) and disorders of immune dysregulation (46/264) (17.4%).…”

Section: Discussionmentioning

confidence: 98%

Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population

et al. 2019

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Objective: To present the genetic causes of patients with primary immune deficiencies (PIDs) in Kuwait between 2004 and 2017.Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. Genomic DNA from patients with clinical and immunological features of PID was sequenced using Sanger sequencing (SS), next generation sequencing (NGS) of targeted genes, whole exome sequencing (WES), and/or whole genome sequencing (WGS). Functional assays were utilized to assess the biologic effect of identified variants. Fluorescence in situ hybridization (FISH) for 22q11.2 deletion and genomic hybridizations arrays were performed when thymic defects were suspected.Results: A total of 264 patients were registered during the study period with predominance of patients with immunodeficiencies affecting cellular and humoral immunity (35.2%), followed by combined immunodeficiencies with associated syndromic features (24%). Parental consanguinity and family history suggestive of PID were reported in 213 (81%) and 145 patients (55%), respectively. Genetic testing of 206 patients resulted in a diagnostic yield of 70%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by in an autosomal recessive pattern. The majority of the mutations were missense mutations (57%) followed by deletions and frame shift mutations. Five novel disease-causing genes were discovered.Conclusions: Genetic testing should be an integral part in the management of primary immunodeficiency patients. This will help the delivery of precision medicine and facilitate proper genetic counseling. Studying inbred populations using sophisticated diagnostic methods can allow better understanding of the genetics of primary immunodeficiency disorders.

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Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Cited by 37 publications

References 36 publications

The Kuwait National Primary Immunodeficiency Registry 2004–2018

The Kuwait National Primary Immunodeficiency Registry 2004–2018

Update on Infections in Primary Antibody Deficiencies

Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population

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