Genetic mutations and immunological features of severe combined immunodeficiency patients in Iran

Shahbazi, Zahra; Yazdani, Reza; Shahkarami, Sepideh; Shahbazi, Shirin; Hamid, Mohammad; Sadeghi‐Shabestari, Mahnaz; Momen, Tooba; Aleyasin, Soheila; Esmaeilzadeh, Hossein; Darougar, Sepideh; Delavari, Sama; Mahdaviani, Seyed Alireza; Ahanchian, Hamid; Behmanesh, Fatemeh; Kiaee, Fatemeh; Chavoshzade, Zahra; Shariat, Mansoureh; Keramatipour, Mohammad; Rezaei, Nima; Abolhassani, Hassan; Parvaneh, Nima; Mahdian, Reza; Aghamohammadi, Asghar

doi:10.1016/j.imlet.2019.10.001

Cited by 15 publications

(18 citation statements)

References 30 publications

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“…This is similar to reports from several other countries where consanguinity rates are high ( Table 6 ) ( 7 , 8 , 51 – 59 ). Though consanguinity rate of 28.2% observed in our study is lower than that of Saudi Arabia and Iran, practice of endogamous and intra-community marriages is, perhaps, responsible for high proportion of autosomal recessive forms of SCID in India ( 2 , 6 ). Median age at diagnosis of SCID in our study is 5 months.…”

Section: Discussioncontrasting

confidence: 63%

“…Molecular defects in SCID can be broadly classified as abnormalities in VDJ recombination ( RAG1, RAG2 , DCLRE1C, NHEJ1, LIG4, PRKDC ), abnormalities of cytokine signaling ( IL2RG, JAK3, IL7RA ), toxic metabolite accumulation ( ADA, PNP ), defective survival of hematopoietic precursors ( AK2, RAC2 ), abnormalities of T-cell receptor and signaling ( PTPRC, CD3D, CD3E, CD3Z, LAT ), and abnormalities of actin cytoskeleton ( CORO1A ). While X-linked SCID due to defect in IL2RG is considered to be the commonest form of SCID in the US, Canada, and Europe, autosomal recessive form of SCID due to defects in RAG1/2 are the commonest forms of SCID in countries where consanguinity rates are high ( 6 – 8 ). However, after initiation of newborn screening program, defects in RAG1/RAG2 are now increasingly being identified even in countries like US and Canada where consanguinity rates are low ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…Being a tropical nation with universal coverage of BCG vaccination in newborns, microbiological pattern of infections in SCID in India is expected to be different from other cohorts. Molecular spectrum is also expected to be different considering high rates of consanguinity and endogamous marriages in India ( 6 – 8 ). A recent cohort of 57 patients from Mumbai, India showed a high incidence of autosomal recessive forms of SCID with RAG1/2 defects being the commonest ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

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Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Vignesh¹,

Rawat²,

Kumrah³

et al. 2021

Front. Immunol.

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BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.

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Section: Discussioncontrasting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Vignesh¹,

Rawat²,

Kumrah³

et al. 2021

Front. Immunol.

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“…2004 [1]. Also, patient 7 had a variant Val722Ile in the JH2 domain that had been previously reported in a homozygous phenotype in a patient from Iran [18] and in a patient with compound heterozygote phenotype in the United States [1]. The JH2 pseudokinase domain is catalytically inactive, but influences the activity of various JAK proteins.…”

Section: Discussionmentioning

confidence: 95%

“…None of the patients having received the BCG vaccine or the OPV developed related complications; this contrasts with Shahbazi et al .’s observation [18] of BCG‐related complications in 40% of their patients. The latter researchers reported that BCGosis was the first symptom in 31·4% of the patients, and that 7% of tested cases shed poliovirus.…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing of T-B+ severe combined immunodeficiency in Egyptian infants, JAK3 predominance and novel variants

Hawary

Meshaal

Mauracher

et al. 2020

Clinical and Experimental Immunology

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The clinical manifestations in the T‐B+SCID patients includes failure to thrive, oral ‎candidiasis, diarrhea, pneumonia, napkin dermatitis, skin rash, otitis media and ‎meningitis. ‎ Genetic analysis of T‐B+ Egyptian SCID patients revealed variants in JAK3 gene in ‎‎60% of the patients, IL2RG in 30%, IL7RA in 5% and CD3E in 5%. ‎JAK3 gene should be sequenced in all T‐B+ patients especially if X SCID is ruled out ‎in male patients by analyzing the family’s pedigree, medical history and Sanger ‎sequencing.‎

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Diagnostic yield of next-generation sequencing in suspect primary immunodeficiencies diseases: a systematic review and meta-analysis

Chen,

Li,

Yin

et al. 2024

Clin Exp Med

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To determine the diagnostic yield of Next-generation sequencing (NGS) in suspect Primary Immunodeficiencies Diseases (PIDs). This systematic review was conducted following PRISMA criteria. Searching Pubmed and Web of Science databases, the following keywords were used in the search: (“Next-generation sequencing”) OR “whole exome sequencing” OR “whole genome sequencing”) AND (“primary immunodeficiency disease” OR “PIDs”). We used STARD items to assess the risk of bias in the included studies. The meta-analysis included 29 studies with 5847 patients, revealing a pooled positive detection rate of 42% (95% CI 0.29–0.54, P < 0.001) for NGS in suspected PID cases. Subgroup analyses based on family history demonstrated a higher detection rate of 58% (95% CI 0.43–0.71) in patients with a family history compared to 33% (95% CI 0.21–0.46) in those without (P < 0.001). Stratification by disease types showed varied detection rates, with Severe Combined Immunodeficiency leading at 58% (P < 0.001). Among 253 PID-related genes, RAG1, ATM, BTK, and others constituted major contributors, with 34 genes not included in the 2022 IUIS gene list. The application of NGS in suspected PID patients can provide significant diagnostic results, especially in patients with a family history. Meanwhile, NGS performs excellently in accurately diagnosing disease types, and early identification of disease types can benefit patients in treatment.

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Genetic mutations and immunological features of severe combined immunodeficiency patients in Iran

Cited by 15 publications

References 30 publications

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Whole-exome sequencing of T-B+ severe combined immunodeficiency in Egyptian infants, JAK3 predominance and novel variants

Diagnostic yield of next-generation sequencing in suspect primary immunodeficiencies diseases: a systematic review and meta-analysis

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