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A single adult patient born to consanguineous parents was found to harbor a homozygous frameshift variant in TNFSF13, encoding APRIL, underlying autosomal recessive common variable immunodeficiency (CVID). APRIL mRNA and protein were undetectable in patient monocytes and iPSC-derived dendritic cells, and circulating plasmacytes were markedly reduced while marginal zone B cells were increased, resulting in hypogammaglobulinemia and decreased antibody levels ([HP:0004313]). In vitro, memory B‐cell differentiation into plasmacytes was impaired but fully rescued by recombinant APRIL supplementation, confirming a loss‐of‐function mechanism and APRIL’s essential role in lifelong plasmacyte maintenance and immunoglobulin production ([PMID:32298700]).
Gene–Disease AssociationLimitedSingle homozygous LoF proband with APRIL deficiency, no additional unrelated families ([PMID:32298700]) Genetic EvidenceLimitedOne patient with biallelic frameshift variant segregating in a consanguineous family ([PMID:32298700]) Functional EvidenceModerateAbsent APRIL expression in patient cells; impaired plasmacyte differentiation rescued by recombinant APRIL ([PMID:32298700]) |