Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: MCTS1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Green List (high evidence)

Comment on list classification: As reviewed by Boaz Palterer, there is sufficient evidence available (five unrelated cases) for the association of hemizygous MCTS1 variants with MSMD. Hence, this gene can be promoted to green rating in the next GMS review.

Created: 5 Jan 2024, 6:45 p.m. | Last Modified: 5 Jan 2024, 6:45 p.m.

Panel Version: 4.155

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Inherited susceptibility to mycobacterial diseases, MONDO:0019146

Publications

• 37875108

Green List (high evidence)

Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria
https://doi.org/10.1016/j.cell.2023.09.024

Bohlen et al. identified 6 male subjects from 5 kindreds with LOF MCTS-1 variants with MSMD.
Extensive ex-vivo functional validation and mouse model.
Sources: Literature

Created: 24 Oct 2023, 7:46 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
MSMD; non tubercular mycobacteria infection; BCGtis; BCG infection