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Intellectual disability

Gene: USP18

Red List (low evidence)

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

1 review

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Total 3 families, 6 patients, with functional evidence.

Family 1: 3 sibs with homozygous truncating mutation in the USP18 gene, segregated with the disorder in the family.
Family 2: 2 sibs with compound heterozygous mutations.
Cells from patients in both families showed complete absence of the USP18 protein. Patient fibroblasts showed enhanced induction of IFN-stimulated transcripts after stimulation with alpha-IFN compared to controls, and transduction of patient cells with wildtype USP18 rescued these effects at the mRNA and protein level. The findings indicated that the disorder results from an aberrant response to type I IFN, rather than an increase in expression of IFN itself.

Family 3: 1 patient with homozygous splice site variant in the USP18 gene This patient had stable mRNA (with skipping of exon 10), and functional studies showed that the mechanism of the mutation was not USP18 deficiency but lack of its ability to stabilize ISG15 (147571) and thereby suppress interferon signaling.
Created: 2 Mar 2020, 5:09 a.m. | Last Modified: 2 Mar 2020, 5:09 a.m.
Panel Version: 3.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pseudo-TORCH syndrome 2, OMIM #617397

Publications

History Filter Activity

29 Sep 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: USP18 was added gene: USP18 was added to Intellectual disability. Sources: Victorian Clinical Genetics Services Mode of inheritance for gene: USP18 was set to