Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: NUDCD3

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:34 p.m. | Last Modified: 26 Sep 2024, 3:34 p.m.

Panel Version: 6.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: Although all four unrelated families harboured the same variant, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 26 Jun 2024, 8:12 p.m. | Last Modified: 26 Jun 2024, 8:14 p.m.

Panel Version: 5.5

PMID:38787962 reported 11 patients across four consanguineous kindreds with a single deleterious missense variant in NUDCD3 gene in homozygous state. Two infants had severe combined immunodeficiency with the complete absence of T and B cells), whereas nine showed classical features of Omenn syndrome.

Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro. 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.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 26 Jun 2024, 7:49 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe combined immunodeficiency, MONDO:0015974; Omenn syndrome, MONDO:0011338

Publications

• 38787962