Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: USP18

The rating of this gene has been updated following NHS Genomic Medicine Service approval. Additional comments from NTGLH: '73.7% Pseudogene exons 3-10 >98% homology ex11 excluded from analysis'

Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.

Panel Version: 2.529

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 3:47 p.m. | Last Modified: 20 Oct 2020, 3:47 p.m.

Panel Version: 2.364

Comment on list classification: Promoted from Amber to Green based on expert reviews.

Created: 15 Apr 2020, 3:22 p.m. | Last Modified: 15 Apr 2020, 3:22 p.m.

Panel Version: 2.70

Green List (high evidence)

Three unrelated families reported. Note cryptic 3' deletion identified in one. We have included this gene on our 'systemic auto inflammatory disease' panel (as well as a number of other panels aimed at the principal presenting features). As other similar disorders such as Aicardi-Goutieres syndrome are included in the PID panel, there is an argument to be made about consistency.

Created: 12 Apr 2020, 4:31 a.m. | Last Modified: 12 Apr 2020, 4:31 a.m.

Panel Version: 2.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pseudo-TORCH syndrome 2, MIM# 617397

Publications

• 31940699
• 27325888

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Agree with Tracy, very high confidence that mutations in this gene cause severe pseudo-TORCH picture

Created: 23 Oct 2019, 7 a.m. | Last Modified: 23 Oct 2019, 7 a.m.

Panel Version: 1.132

I don't know

agree with all the Amber genes

Created: 25 Sep 2019, 1:49 p.m. | Last Modified: 25 Sep 2019, 1:49 p.m.

Panel Version: 1.115

Green List (high evidence)

I think USP18 should be green: five PTS patients from two unrelated families

Created: 26 Sep 2019, 12:43 p.m. | Last Modified: 26 Sep 2019, 12:43 p.m.

Panel Version: 1.127

The amber genes are covered on our targeted exome, we feel that these should be covered in the testing

Created: 25 Sep 2019, 1:44 p.m. | Last Modified: 25 Sep 2019, 1:44 p.m.

Panel Version: 1.114

I don't know

Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber.

Created: 12 Nov 2019, 5:04 p.m. | Last Modified: 12 Nov 2019, 5:04 p.m.

Panel Version: 1.137

Pseudo TORCH syndrome: Aicardi-Goutiere like - severe intracranial haemorrhage, thrombocytopaenia, seizures, liver failure caused by interferon activation - probable green association, is it a relevant phenotype?
2 families (one homozygous, one compound het where one variant was the same as the first family with possible common ancestor) - borderline, with lack of USP18 expression - abnormal activation of the immune system (interferon) - is this a likely presentation in immunology clinic?

Created: 26 Sep 2019, 4 p.m. | Last Modified: 26 Sep 2019, 4 p.m.

Panel Version: 1.130

Comment on list classification: Changed rating from Red to Amber to reflect the agreed rating agreed by the GMS Immunology Specialist Test Group, but flagged for further follow up with the Immunology Test Group due to the subsequent conflicting review. Evidence /opinion needs consensus before upgrading to Green

Created: 26 Sep 2019, 10:59 a.m. | Last Modified: 26 Sep 2019, 1:13 p.m.

Panel Version: 1.127

Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. Although discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 to rate Amber in the confirmed follow up email on 20th June North West GLH reasserted that USP18 should be Green

Created: 25 Sep 2019, 3 p.m. | Last Modified: 26 Sep 2019, 1:13 p.m.

Panel Version: 1.127

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 only enough evidence to rate this gene Amber

Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.

Panel Version: 1.116

Comment on publications: Added publications PMID: 31272490, PMID:27325888 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. : five PTS patients from two unrelated families. Flagged for further discussion with the Specialist Test Group as conflicts with the Amber rating agreed in the webex 28th March 2019

Created: 15 Aug 2019, 4:30 p.m. | Last Modified: 15 Aug 2019, 4:55 p.m.

Panel Version: 1.51

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): USP18 .PanelApp HGNC gene symbol check: USP18 . IUIS Disease: USP18 deficiency . IUIS Inheritance: AR , .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: TORCH like syndrome. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Type 1 Interferonopathies

Created: 6 Jul 2018, 12:23 p.m.