NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome.
Sci Immunol
; 9(95): eade5705, 2024 May 24.
Article
en En
| MEDLINE
| ID: mdl-38787962
ABSTRACT
Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain-containing 3 (NUDCD3). Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T -B- SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inmunodeficiencia Combinada Grave
/
Recombinación V(D)J
Límite:
Animals
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Sci Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido