Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: DOCK11

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: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.

Created: 30 Aug 2023, 1:19 p.m. | Last Modified: 30 Aug 2023, 1:20 p.m.

Panel Version: 4.29

PMID:3695263 - Eight male patients from seven unrelated families with hemizygous DOCK11 missense variants presented with early-onset autoimmunity, including cytopenia, systemic lupus erythematosus, skin, and digestive manifestations. Of these, fourth patients had digestive manifestations such as severe inflammatory bowel disease (ileo-colitis), colon cryptitis, ileitis, oral and anal ulcers and intermittent diarrhoea.

PMID:37342957 - Four unrelated male patients with germline DOCK11 variants presented with early-onset immune dysregulation and haematopoietic defects of unknown origin. All four patients had infections and two had gastrointestinal manifestations. In addition, functional studies from both patient-derived and DOCK11-knockout mouse, and zebrafish model support the phenotypes observed in patients.

This gene has been associated with relevant phenotypes in OMIM (MIM #301109), but not yet in Gene2Phenotype.

Created: 30 Aug 2023, 1:18 p.m. | Last Modified: 30 Aug 2023, 1:18 p.m.

Panel Version: 4.26

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

Phenotypes
Autoinflammatory disease, multisystem, with immune dysregulation, X-linked, OMIM:301109

Publications

• 36952639
• 37342957

Green List (high evidence)

Boussard et al. described 8 male patients, from 7 unrelated families, with hemizygous DOCK11 missense variants leading to reduced DOCK11 expression. The patients presented with early-onset autoimmunity, including cytopenia, systemic lupus erythematosus, skin, and digestive manifestations. Extensive ex vivo and in vitro functional validation.
Sources: Literature

Created: 22 Jun 2023, 4:14 p.m.

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

Phenotypes
early-onset autoimmunity; cytopenia; systemic lupus erythematosus; dermatitis; enteropathy

Publications

• 36952639