Human BCL10 Deficiency due to Homozygosity for a Rare Allele

In 2014, a child with broad combined immunodeficiency (CID) who was homozygous for a private BCL10 allele was reported to have complete inherited human BCL10 deficiency. In the present study, we report a new BCL10 mutation in another child with CID who was homozygous for a BCL10 variant (R88X), prev...

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Bibliographic Details
Published in:Journal of clinical immunology 2020-02, Vol.40 (2), p.388-398
Main Authors: Van Den Rym, Ana, Taur, Prasad, Martinez-Barricarte, Rubén, Lorenzo, Lazaro, Puel, Anne, Gonzalez-Navarro, Pablo, Pandrowala, Ambreen, Gowri, Vijaya, Safa, Amin, Toledano, Victor, Cubillos-Zapata, Carolina, López-Collazo, Eduardo, Vela, Maria, Pérez-Martínez, Antonio, Sánchez-Ramón, Silvia, Recio, Maria J., Casanova, Jean-Laurent, Desai, Mukesh M., Perez de Diego, Rebeca
Format: Article
Language:English
Subjects:
Alleles
Bcl-10 protein
Biomedical and Life Sciences
Biomedicine
Colitis
Fibroblasts
Gastroenteritis
Gene frequency
Immunodeficiency
Immunological memory
Immunology
Infectious Diseases
Internal Medicine
Lymphocytes T
Medical Microbiology
Memory cells
Mutants
Original Article
Phenotypes
TLR2 protein
TLR4 protein
Toll-like receptors
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Summary:In 2014, a child with broad combined immunodeficiency (CID) who was homozygous for a private BCL10 allele was reported to have complete inherited human BCL10 deficiency. In the present study, we report a new BCL10 mutation in another child with CID who was homozygous for a BCL10 variant (R88X), previously reported as a rare allele in heterozygosis (minor allele frequency, 0.000003986). The mutant allele was a loss-of-expression and loss-of-function allele. As with the previously reported patient, this patient had complete BCL10 deficiency. The clinical phenotype shared features, such as respiratory infections, but differed from that of the previous patient that he did not develop significant gastroenteritis episodes or chronic colitis. Cellular and immunological phenotypes were similar to those of the previous patient. TLR4, TLR2/6, and Dectin-1 responses were found to depend on BCL10 in fibroblasts, and final maturation of T cell and B cell maturation into memory cells was affected. Autosomal-recessive BCL10 deficiency should therefore be considered in children with CID.
ISSN:0271-9142
1573-2592
DOI:10.1007/s10875-020-00760-3