A Novel RAG1 Mutation in a Compound Heterozygous Status in a Child With Omenn Syndrome

Shen, Juan; Jiang, Li; Gao, Yifang; Ou, Rongqiong; Yu, S.; Yang, Baofeng; Wu, Changyou; Tan, Weiping

doi:10.3389/fgene.2019.00913

Cited by 6 publications

(3 citation statements)

References 25 publications

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“…RAG1 gene is significantly involved in the initiation of recombination process of the V, (D), and J segments, which finally form the variable portions of immunoglobulin and TCR proteins. 9 Germline mutations in RAG1 gene causes profound reduction of T and B cells, leads to the occurrence of OS. 1 OS is extremely rarest types of SCID, usually manifested with gradually and progressively increased oligoclonal and activated T cells, with absence of B lymphocytes, which in turn results into the clinical phenotype including generalized erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, and elevated level of serum IgE.…”

Section: Discussionmentioning

confidence: 99%

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Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome

Wang

Wang²,

Wang³

et al. 2022

Allergol Immunopathol

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Introduction and objectives: Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymphadenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human RAG1 gene cause OS. Materials and methods: In this study, we investigated a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure. Parents of the proband were phenotypically normal. Results: Karyotype analysis and chromosomal microarray analysis found no chromosomal struc-tural abnormalities (46, XY) and no pathogenic copy number variations (CNVs) in the proband. Whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene in the proband. Sanger sequencing confirmed that both the proband parents were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters and one elder brother of the proband and in the 100 ethnically matched normal healthy individuals. This novel homozygous deletion (c.2662delC) leads to the frameshift, which finally results in the formation of the truncated protein (p.Leu888Phefs*3) V(D)J recombination-activating protein 1 with 890 amino acids compared with the wildtype V(D)J recombination-activating protein 1 of 1043 amino acids. Hence, it is a loss-of-function variant. Conclusions: Our present study expands the mutational spectrum of the RAG1 gene associated with OS. We also strongly suggested the importance of whole-exome sequencing for the genetic screening of patients with OS.

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Section: Discussionmentioning

confidence: 99%

“…In Chinese population, the incidence rate of OS is very rare and only one OS patient has been reported so far. 9 Here, we analysed and investigated the phenotype and genotype of a children with OS in a nonconsanguineous Chinese family.…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome

Wang

Wang²,

Wang³

et al. 2022

Allergol Immunopathol

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“…Severe combined immunodeficiency (SCID), is a hereditary group of disorders with the highest rate of mortality between the inborn errors of immunity (IEI). 1 The incidence of the disease is one in 40,000 to 75,000 newborns. 2 Both cellular and humoral immune systems can be involved in SCID.…”

Section: Introductionmentioning

confidence: 99%

A novel homozygous RAG1 mutation is associated with severe combined immunodeficiency and neurological presentations

Shafeghat

Esmaeilzadeh

Sadeghalvad

et al. 2021

aei

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Introduction and objectives: Severe combined immunodeficiency (SCID) is a subset of primary immunodeficiency diseases caused by a hereditary deficiency of the adaptive immune system. Mutation in recombination activating gene (RAG) is known as the underlying genetic cause of SCID. RAG protein plays a pivotal role in V(D)J recombination which is the main process to assemble lymphocyte antigen receptors during T- and B-cell development. The patients are characterized by recurrent infections, failure to thrive, chronic diarrhea, and fever, in early infancy. Herein, we present a case of SCID with rare neurological manifestations affected by a mutation in RAG1.Patients and methods: The patient was a 15-month-old infant born to a consanguineous family. She was presented with neurological abnormalities including facial nerve palsy, seizure, and decreased consciousness. Next-generation sequencing (NGS)-based primary immunodeficiency disease (PID)-gene panel screen and Sanger sequencing were performed to identify the genetic mutation.Results: We found a novel homozygous missense mutation in RAG1, c.1210C>T,p.Arg404Trp, which was predicted to be deleterious (combined annotation dependent depletion, CADD score of 27.4). Both parents were heterozygous carriers for this mutation. According to her laboratory data, both T cell and B cell numbers were decreased and the patient was diagnosed as RAG1- SCID.Conclusions: SCID is a pediatric emergency with a variety of manifestations in infants. Therefore, accurate diagnosis importantly in the case of rare manifestations must be considered in these patients. Our findings point toward the importance of genetic assessment for early diagnosis and timely treatment of this disorder.

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Successful bone marrow transplantation in a patient with Omenn syndrome, a rare variant of severe combined immunodeficiency syndrome: A case report

Khan,

Umer,

Muhammad

et al. 2024

Clinical Case Reports

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Key Clinical MessageBone marrow transplantation (BMT) saves lives in Omenn syndrome, a severe immunodeficiency disorder. Timely genetic diagnosis and matched donor BMT are crucial. Emphasis on newborn screening and multidisciplinary care improves outcomes for infants with inherited disorders. Prompt intervention and comprehensive management are vital for a successful transplant outcome.AbstractOmenn syndrome represents a severe variant of combined immunodeficiency characterized by disregulated immune responses and susceptibility to recurrent infections. We present the case of a 3‐month‐old female infant initially presenting with upper respiratory infection symptoms and a diffuse rash, unresponsive to local treatment. At 4 months of age, the patient underwent allogeneic bone marrow transplantation (BMT) utilizing stem cells from a fully matched sibling donor. Pre‐transplant conditioning included antimicrobial prophylaxis and supportive therapies. Following BMT, the patient received immunosuppressive medications to prevent graft rejection and graft‐versus‐host disease. Clinical monitoring post‐transplant showed timely neutrophil and platelet engraftment, with subsequent follow‐up demonstrating stable clinical parameters and negative cytomegalovirus status. The case highlights the importance of timely diagnosis and treatment in managing severe immunodeficiency disorders, demonstrating the potential for successful outcomes with appropriate timely interventions. Regular monitoring and follow‐up appointments were crucial in ensuring the success of the treatment. This case also emphasizes the significance of multidisciplinary care and genetic testing in identifying and managing rare immunodeficiency disorders. The successful outcome in this case provides hope for improved treatment options and better patient outcomes in the future.

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A Novel RAG1 Mutation in a Compound Heterozygous Status in a Child With Omenn Syndrome

Cited by 6 publications

References 25 publications

Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome

Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome

A novel homozygous RAG1 mutation is associated with severe combined immunodeficiency and neurological presentations

Successful bone marrow transplantation in a patient with Omenn syndrome, a rare variant of severe combined immunodeficiency syndrome: A case report

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