Details

Autor(en) / Beteiligte

• Chen, Rui
• Lukianova, Elena
• van der Loeff, Ina Schim
• Spegarova, Jarmila Stremenova
• Willet, Joseph D P
• James, Kieran D
• Ryder, Edward J
• Griffin, Helen
• IJspeert, Hanna
• Gajbhiye, Akshada
• Lamoliatte, Frederic
• Marin-Rubio, Jose L
• Woodbine, Lisa
• Lemos, Henrique
• Swan, David J
• Pintar, Valeria
• Sayes, Kamal
• Ruiz-Morales, Elias R
• Eastham, Simon
• Dixon, David
• Prete, Martin
• Prigmore, Elena
• Jeggo, Penny
• Boyes, Joan
• Mellor, Andrew
• Huang, Lei
• van der Burg, Mirjam
• Engelhardt, Karin R
• Stray-Pedersen, Asbjørg
• Erichsen, Hans Christian
• Gennery, Andrew R
• Trost, Matthias
• Adams, David J
• Anderson, Graham
• Lorenc, Anna
• Trynka, Gosia
• Hambleton, Sophie

Titel

NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome

Ist Teil von

• Science immunology, 2024-05, Vol.9 (95), p.eade5705

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ( ) 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.