Novel Compound Heterozygous Mutations in RAG1 in a Patient with Cutaneous Lymphoproliferative Disease

Xu, Congcong; Chen, Ming Zhi; Xiong, Jingshu; Gan, Lu; Zhang, Ying; Chen, Hao; Sun, Jianfang

doi:10.2340/00015555-3042

Cited by 1 publication

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References 10 publications

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“…These patients had only two types of neoplasms: DLBCL (three cases) and cutaneous lymphoproliferative disease (CLPD) (three cases). CLPD manifested at a later age (2.5, 5, and 15 years) in patients with milder phenotype, which can be described as combined immunodeficiency or “leaky” SCID ( 20 , 21 ). In contrast, DLBCL manifested earlier: in two cases, the diagnosis was established in the first year of life and occurred even in patients with typical SCID phenotype ( 17 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

Infant with diffuse large B-cell lymphoma identified postmortem with homozygous founder Slavic RAG1 variant: a case report and literature review

Volodashchik,

Polyakova,

Mikhaleuskaya

et al. 2024

Front. Pediatr.

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Background and aimsThere is an increased risk of lymphomas in inborn errors of immunity (IEI); however, germline genetic testing is rarely used in oncological patients, even in those with early onset of cancer. Our study focuses on a child with a recombination-activating gene 1 (RAG1) deficiency who was identified through a screening program for Slavic founder genetic variants among patients who died with malignancy at an early age in Belarus.ResultsWe identified one homozygous founder RAG1 variant out of 24 available DNA samples from 71 patients who developed lymphoma aged <3 years from the Belarusian cancer registry between 1986 and 2023. Our patient had an episode of pneumonia at 3 months of age and was hospitalized for respiratory distress, candida-positive lung disease, and lymphadenopathy at 14 months of age. The diagnosis of Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) was established. The patient had a normal lymphocyte count that decreased over time. One month after chemotherapy initiation, the patient died due to sepsis and multiple organ failure without a genetic diagnosis. In a retrospective analysis, T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) were undetectable in peripheral blood.ConclusionsA targeted screening program designed to detect a Slavic founder variant in the RAG1 gene among children revealed a 14-month-old Belarusian male infant with low TREC levels who died of EBV-driven DLBCL and complications of chemotherapy including infections. This case highlights how patients with IEI and recurrent infections may develop serious non-infectious complications, such as fatal malignancy. It also emphasizes the importance of early identification, such as newborn screening for severe combined immune deficiency. Earlier diagnosis of RAG deficiency could have prompted hematopoietic stem cell transplant well before the DLBCL occurrence. This likely would impact the onset and/or management strategies for the cancer.

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