Fetal anomalies
Gene: USP18

USP18 (ubiquitin specific peptidase 18)
EnsemblGeneIds (GRCh38): ENSG00000184979
EnsemblGeneIds (GRCh37): ENSG00000184979
OMIM: 607057, Gene2Phenotype
USP18 is in 9 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.

Panel Version: 1.836

Comment on list classification: With addition of the recently reported case (PMID:31940699) there is now a total of three families with pseudo-TORCH syndrome due to biallelic variants in USP18 (two carrying the same founder variant).

A rating upgrade from Amber to Green should be considered and therefore this gene will be flagged for review at the date of next GMS panel update (added 'for-review' tag).
Created: 9 Oct 2020, 10:24 a.m. | Last Modified: 9 Oct 2020, 10:24 a.m.

Panel Version: 1.104

Added 'treatable' tag as clinical remission was achieved in a patient following rapid genetic diagnosis and subsequent treatment with the JAK inhibitor ruxolitinib
Created: 9 Oct 2020, 10:20 a.m. | Last Modified: 9 Oct 2020, 10:20 a.m.

Panel Version: 1.103

- PMID: 31940699 (2020) - One additional unrelated case - Saudi Arabian boy with a homozygous splice-site variant (c.1073+1G>A) in USP18, presented pseudo-TORCH syndrome characterised by hydrocephalus with seizures, intraventricular haemorrhage, brain calcifications, necrotizing cellulitis, systemic inflammation, multiple organ failure, and respiratory failure. This was the only patient to survive beyond the perinatal period owing to supportive care and prompt treatment with ruxolitinib. At the time of publication, the child was 3-years-old and was in full remission of clinical manifestations while continuing to receive oral ruxolitinib. He continues to grow normally, however authors note delay in developmental milestones.
Created: 9 Oct 2020, 10:19 a.m. | Last Modified: 9 Oct 2020, 10:19 a.m.

Panel Version: 1.103

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pseudo-TORCH syndrome 2, 617397

Publications

31940699

Created: 9 Oct 2020, 10:19 a.m.
Last Modified: 9 Oct 2020, 10:19 a.m.
Panel version: 1.836

Rebecca Foulger (Genomics England curator)

I don't know

Kept rating as Amber on advice from Anna de Burca (Genomics England Clinical Team): fetally releavant phenotype but insufficient evidence for Green rating.
Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.

Panel Version: 0.311

Rated as 'Probable' in original PAGE list. Rated green on 'Intracerebral calcification disorders' panel and phenotype (pseudo-TORCH syndrome) is appropriate for Fetal panel, as noted by Helen Brittain and Anna de Burca (Genomics England Clinical team). However, kept rating as Amber for now based on insufficient evidence to support causation: One publication (Meuwissen et al. 2016, PMID:27325888) with two families (Turkish and German) with pseudo-TORCH syndrome-2 and homozygous or compound het variants in USP18. Segregation shown in 5 affected individuals plus an unaffected sibling. Cells from patients in both families showed complete absence of the USP18 protein.
Created: 22 Jan 2019, 9:07 a.m.

DDG2P rating in original PAGE list: Probable for Severe pseudo-TORCH syndrome
Created: 11 Dec 2018, 9:05 a.m.

Phenotypes
Pseudo-TORCH syndrome 2, 617397

Publications

27325888

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.311

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Pseudo-TORCH syndrome 2, 617397

Tags

treatable

OMIM

607057

Clinvar variants

Variants in USP18

Penetrance

None

Publications

Panels with this gene