Adult-Onset Myopathy in a Patient with Hypomorphic RAG2 Mutations and Combined Immune Deficiency

Henrickson, Sarah E.; Walter, Jolán E.; Quinn, Colin; Kanakry, Jennifer A.; Bardakjian, Tanya; Dimitrova, Dimana; Ujházi, Boglárka; Csomós, Krisztián; Bosticardo, Marita; Dobbs, Kerry; Nasrallah, MacLean P.; Notarangelo, Luigi D.; Holland, Steven M.; Fadugba, Olajumoke

doi:10.1007/s10875-018-0538-3

Cited by 3 publications

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References 15 publications

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“…There is still concern for progressive inflammatory lung disease, or occurrence of autoimmune complication, as reported by our group (10). Only a selected number of adolescent and adults with partial RAG deficiency received HSCT with variable success (21, 22). Allogeneic HSCT is a viable option for our patient; we are discussing with the family whether it is worthwhile given the patient's good response to current treatment vs. the risk of potential inflammatory and/or autoimmune sequela.…”

Section: Discussionmentioning

confidence: 99%

Combined Immunodeficiency With Late-Onset Progressive Hypogammaglobulinemia and Normal B Cell Count in a Patient With RAG2 Deficiency

et al. 2019

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Proteins expressed by recombination activating genes 1 and 2 (RAG1/2) are essential in the process of V(D)J recombination that leads to generation of the T and B cell repertoires. Clinical and immunological phenotypes of patients with RAG deficiencies correlate well to the degree of impaired RAG activity and this has been expanding to variants of combined immunodeficiency (CID) or even milder antibody deficiency syndromes. Pathogenic variants that severely impair recombinase activity of RAG1/2 determine a severe combined immunodeficiency (SCID) phenotype, whereas hypomorphic variants result in leaky (partial) SCID and other immunodeficiencies. We report a patient with novel pathogenic compound heterozygous RAG2 variants that result in a CID phenotype with two distinctive characteristics: late-onset progressive hypogammaglobulinemia and highly elevated B cell count. In addition, the patient had early onset of infections, T cell lymphopenia and expansion of lymphocytes after exposure to herpes family viruses. This case highlights the importance of considering pathogenic RAG variants among patients with preserved B cell count and CID phenotype.

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Section: Discussionmentioning

confidence: 99%