Adulthood diagnosis of Nijmegen breakage syndrome in twins with antibody deficiency clinical presentation

Résumé fourni par la source

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive DNA repair disorder within the spectrum of inborn errors of immunity (IEI), characterized by immunodeficiency and cancer predisposition and typically diagnosed in childhood. We report a pair of 21-year-old monozygotic twins presenting with recurrent infections, hypogammaglobulinemia, ovarian dysfunction, and, in one twin, peripheral T-cell lymphoma. Both carried two novel compound heterozygous variants in the NBN gene (c.657dupA and c.1064_1124 + 9del). Immunophenotyping revealed reduced memory B cells, impaired vaccine responses, and low lymphoproliferation. Functional γ-H2AX assays demonstrated defective DNA damage response following ionizing radiation, supporting the pathogenicity of the identified variants, which were also predicted as deleterious by in silico analysis and shown to segregate in trans. These findings expand the genotypic spectrum of NBS and demonstrate that compound heterozygosity for non-classical NBN variants can lead to an adult identification of the disease. These cases highlight the importance of integrating genetic and functional analyses to facilitate the recognition of DNA repair disorders beyond childhood and to guide appropriate clinical surveillance and management.

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