Variants in IGLL1 cause a broad phenotype from agammaglobulinemia to transient hypogammaglobulinemia.

BACKGROUND

Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only eight documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1.

OBJECTIVE

To provide a comprehensive overview of the clinical and immunological findings of patients with B-cell deficiency attributed to variants in IGLL1.

METHODS

NBS programs reporting using kappa-deleting recombination excision circle assays, the European Society for Immunodeficiencies Registry, and authors of published reports featuring patients with B-cell deficiency linked to IGLL1 variants were contacted. Only patients with (likely) pathogenic variants, reduced CD19+ counts and no alternative diagnosis were included.

RESULTS

The study included 13 patients identified through NBS, two clinically diagnosed patients, and two asymptomatic siblings. All had severely reduced CD19+ B-cells (< 0.1×10

CONCLUSION

B-cell deficiency resulting from IGLL1 variants appears to be more prevalent than initially believed. Despite markedly low B-cell counts, the clinical course in some patients may be milder than reported in the literature so far.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.