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Early onset or syndromic epilepsy

Gene: USP18

Green List (high evidence)

USP18 (ubiquitin specific peptidase 18)
EnsemblGeneIds (GRCh38): ENSG00000184979
EnsemblGeneIds (GRCh37): ENSG00000184979
OMIM: 607057, Gene2Phenotype
USP18 is in 10 panels

2 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.
Panel Version: 2.491

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update - seizures reported in all families described to date.
Created: 8 Oct 2020, 4:11 p.m. | Last Modified: 8 Oct 2020, 4:11 p.m.
Panel Version: 2.164
Added 'treatable' tag as clinical remission was achieved in a patient following rapid genetic diagnosis and subsequent treatment with the JAK inhibitor ruxolitinib
Created: 8 Oct 2020, 4:09 p.m. | Last Modified: 8 Oct 2020, 4:09 p.m.
Panel Version: 2.163
- PMID: 27325888 (2016) - Three sibs from a consanguineous Turkish family with a homozygous variant (c.652C>T, p.Q218X) in USP18. Antenatal presentation in one sib led to termination of pregnancy at 22 wk of gestation, and in the remaining two children presentation was neonatal and resulted in death within 2 weeks of life. In the latter two individuals manifestations included severe intracerebral haemorrhages, liver dysfunction, ascites, and lactic acidosis. One sib additionally had severe thrombocytopenia with petechiae, while the other developed seizures.

Two German sibs, previously reported in PMID: 12833411 (2013), were found to be compound het for the same p.Q218X variant and a cryptic 3-prime deletion of the USP18 gene. They presented thrombocytopenia, petechiae, ascites, hepatomegaly, and systemic calcifications. Within the first days of life, they developed seizures and died from severe cerebral haemorrhage.

Haplotype analysis of the region containing the Q218X mutation suggested a common ancestor between the 2 families and a founder effect.

- PMID: 31940699 (2020) - One Saudi Arabian boy with a homozygous splice-site variant (c.1073+1G>A) in USP18, presented 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.
Sources: Literature
Created: 8 Oct 2020, 4:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Pseudo-TORCH syndrome 2, 617397


History Filter Activity

3 Mar 2022, Gel status: 3

Removed Tag

Sarah Leigh (Genomics England Curator)

Tag for-review was removed from gene: USP18.

3 Mar 2022, Gel status: 3

Added New Source, Status Update

Sarah Leigh (Genomics England Curator)

Source Expert Review Green was added to USP18. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

8 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: usp18 has been classified as Amber List (Moderate Evidence).

8 Oct 2020, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: USP18 was added gene: USP18 was added to Genetic epilepsy syndromes. Sources: Literature treatable, for-review tags were added to gene: USP18. Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP18 were set to 12833411; 27325888; 31940699 Phenotypes for gene: USP18 were set to Pseudo-TORCH syndrome 2, 617397 Review for gene: USP18 was set to GREEN