Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: OTULIN
Comment on mode of inheritance: As reviewed by Boaz Palterer, there is sufficient evidence for the association of monoallelic OTULIN variants to immunodeficiency. Hence, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.Created: 30 Aug 2023, 4:34 p.m. | Last Modified: 30 Aug 2023, 4:34 p.m.
Panel Version: 4.32
There is already sufficient evidence available for the association of biallelic OTULIN variants to auto inflammatory disease involving fever, recurrent pneumonia and diarrhoea and these biallelic variants have already been associated with relevant phenotypes in both OMIM (MIM #617099) and Gene2Phenotype ('definitive' rating in the DD panel).
Three unrelated patients harbouring heterozygous OTULIN variants presented in the first decades of life with severe invasive skin or lung infections due to Staphylococcus aureus. Four additional patients from three unrelated families with heterozygous OTULIN variants were reported with features similar to those of individuals with invasive S. aureus infection, but in whom no infectious agent was identified (PMID:35587511). Monoallelic OTULIN variants have now been associated with phenotype in OMIM (MIM #619986), but not in Gene2Phenotype.Created: 30 Aug 2023, 4:29 p.m. | Last Modified: 30 Aug 2023, 4:29 p.m.
Panel Version: 4.29
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
{Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection}, OMIM:619986; Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Additional phenotype of severe life-threatening staph. aureus infections with partial penetrance (rescued by development of antibodies to staph alpha-toxin) caused by heterozygous LOF mutations of Otulin.
Several kindreds, including family members of patients with ORAS. Phenotype is also present in Cri-du-chat 5p deletion, that encompass the Otulin gene.Created: 22 Jun 2023, 4:33 p.m. | Last Modified: 22 Jun 2023, 4:33 p.m.
Panel Version: 4.22
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
life-threatening staphylococcal disease
Publications
Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 1:38 p.m. | Last Modified: 14 Oct 2020, 1:38 p.m.
Panel Version: 2.290
The following PubMed IDs were added to entity OTULIN: 27559085. These publications have been associated with OMIM phenotype MIM#617099, which is listed for this entity, by the autoinflammation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Publications
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on list classification: 3 unrelated cases of OTULIN variants causing MIM:617099 from PMID:27523608 and PMID:27559085. Confirmed DD-G2P for ORAS syndrome (alternative name for MIM:617099). Symptoms of MIM:617099 include recurrent fevers. PMID:27559085 (Zhou et al 2016) report 2 missense and 1 frameshift mutation in OTULIN in one Pakistani family and 2 Turkish families. The Pakistani family is the same family that is reported in PMID:27523608. PMID:27523608 (Damgaard et al, 2016) report 3 affected members of a consanguineous Pakistani family with MIM:617099. From Rebecca Foulger (review of Periodic fevers panel 15 Aug 2017)Created: 19 Jun 2018, 3:56 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Autoinflammation, panniculitis, and dermatosis syndrome 617099
Publications
Mode of inheritance for gene: OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099; Fever, diarrhoea, dermatitis; Autoinflammatory Disorders to {Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection}, OMIM:619986; Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Publications for gene: OTULIN were set to 27559085; 27523608
Tag Q3_23_MOI tag was added to gene: OTULIN.
Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, 617099; Fever, diarrhea , dermatitis; Autoinflammatory Disorders to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099; Fever, diarrhoea, dermatitis; Autoinflammatory Disorders
Gene: otulin has been classified as Green List (High Evidence).
Source Other was added to OTULIN. Publications for gene OTULIN were updated from 27523608; 27559085 to 27559085; 27523608 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to OTULIN.
Source North West GLH was added to OTULIN.
Source London North GLH was added to OTULIN.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Phenotypes for gene OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, 617099, Fever, diarrhea , dermatitis, Autoinflammatory Disorders
Gene: otulin has been classified as Green List (High Evidence).
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, 617099
IUIS Classification February 2018 was added to OTULIN. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to OTULIN. Panel: Primary immunodeficiency disorders
Gene: otulin has been classified as Green List (High Evidence).
OTULIN was added to Primary immunodeficiency disorders panel. Sources: Expert Review
OTULIN was created by Sarah Leigh