Proteomics

Dataset Information

0

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

ABSTRACT: Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 9 affected patients across 3 consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain containing 3 (NUDCD3). Two infants lacked T and B lymphocytes altogether (T-B- severe combined immunodeficiency, T-B- SCID) while 7 showed classical features of Omenn syndrome. Restricted antigen receptor gene usage by residual T lymphocytes implied impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, associated with pathologic sequestration of RAG1 in nucleoli. A mouse model bearing the homologous variant phenocopied these abnormalities, confirming a conserved, requisite role for NUDCD3 in V(D)J recombination.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, T Cell

SUBMITTER: Matthias Trost  

LAB HEAD: Matthias Trost

PROVIDER: PXD035840 | Pride | 2024-09-27

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
20191011_AG_RuiChen_SDS_EV_R1.raw Raw
20191011_AG_RuiChen_SDS_EV_R2.raw Raw
20191011_AG_RuiChen_SDS_EV_R3.raw Raw
20191011_AG_RuiChen_SDS_SDM_R1.raw Raw
20191011_AG_RuiChen_SDS_SDM_R2.raw Raw
Items per page:
1 - 5 of 10
altmetric image

Publications

<i>NUDCD3</i> deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome.

Chen Rui R   Lukianova Elena E   van der Loeff Ina Schim IS   Spegarova Jarmila Stremenova JS   Willet Joseph D P JDP   James Kieran D KD   Ryder Edward J EJ   Griffin Helen H   IJspeert Hanna H   Gajbhiye Akshada A   Lamoliatte Frederic F   Marin-Rubio Jose L JL   Woodbine Lisa L   Lemos Henrique H   Swan David J DJ   Pintar Valeria V   Sayes Kamal K   Ruiz-Morales Elias R ER   Eastham Simon S   Dixon David D   Prete Martin M   Prigmore Elena E   Jeggo Penny P   Boyes Joan J   Mellor Andrew A   Huang Lei L   van der Burg Mirjam M   Engelhardt Karin R KR   Stray-Pedersen Asbjørg A   Erichsen Hans Christian HC   Gennery Andrew R AR   Trost Matthias M   Adams David J DJ   Anderson Graham G   Lorenc Anna A   Trynka Gosia G   Hambleton Sophie S  

Science immunology 20240524 95

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 (<i>NUDCD3</i>)<i>.</i> Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T<sup> -</sup>B<sup>-</sup> SCID), whereas nine showed classical features of Omenn  ...[more]

Similar Datasets

Genomics RAG Represents a Widespread Threat to the Lymphocyte Genome - (Mnase-seq)
2015-08-06 | E-GEOD-69474 | biostudies-arrayexpress
Transcriptomics RAG Represents a Widespread Threat to the Lymphocyte Genome - (RNA-seq)
2015-08-06 | E-GEOD-69473 | biostudies-arrayexpress
Genomics RAG Represents a Widespread Threat to the Lymphocyte Genome - (ChIP-seq)
2015-08-06 | GSE69475 | GEO
Genomics RAG Represents a Widespread Threat to the Lymphocyte Genome - (Mnase-seq)
2015-08-06 | GSE69474 | GEO
Transcriptomics RAG Represents a Widespread Threat to the Lymphocyte Genome - (RNA-seq)
2015-08-06 | GSE69473 | GEO
Other On-target and Off-target Activities of RAG Are Restricted by Topological Chromatin Domains
2015-09-15 | GSE73007 | GEO
Genomics RAG Represents a Widespread Threat to the Lymphocyte Genome - (ChIP-seq)
2015-08-06 | E-GEOD-69475 | biostudies-arrayexpress
Transcriptomics On-target and Off-target Activities of RAG Are Restricted by Topological Chromatin Domains
2015-09-15 | E-GEOD-73007 | biostudies-arrayexpress
Transcriptomics GFI deficiency in plasmacytoid dendritic cells
2013-04-07 | GSE45837 | GEO
Transcriptomics ROR t directs upregulation of RAG gene expression in DP thymocytes and serves as a multi-faceted regulator of the Tcra repertoire.
2023-02-20 | GSE225627 | GEO