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Genetic epilepsy syndromes

Gene: TRIM8

Green List (high evidence)

TRIM8 (tripartite motif containing 8)
EnsemblGeneIds (GRCh38): ENSG00000171206
EnsemblGeneIds (GRCh37): ENSG00000171206
OMIM: 606125, Gene2Phenotype
TRIM8 is in 2 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AD Epileptic encepalopathy - paper by Assoum et al, AJMG, 2018. 6 unrelated patients discussed in total with TRIM8 variants - fs/nonesense variants - all de novo and clustered close together in the C-terminal.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
epileptic encephalopathy

Publications

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Updated rating from Amber to Green based on recent publication: 6 unrelated cases of patients with EE and TRIM8 variants reviewed by the recent PMID:30244534 (includes the two cases previously reported cases in PMID:27346735 and PMID:23934111 plus 4 new cases). Therefore sufficient evidence to support inclusion on diagnostic panel.
Created: 3 Nov 2018, 11:29 a.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 30244534 is a collaborative study reporting on the phenotype of TRIM8-related epileptic encephalopathy and summarizing the findings in previously published patients. Developmental delay, intellectual disability, seizures are common findings in the 6 unrelated individuals reported. Proteinuria was observed in 3 subjects.

Seizures were universal feature with highly variable age of onset (2 months to 3 years and 5 months).

Several individuals were investigated for developmental delay prior to seizure onset (eg. pat.1 had an MRI at 10 months, sat at 16 months, walked at 22 months and developed seizures at 2 years, pat.3 sat at 12 months, walked at 22 and developed seizures at 3 years and 5 months, pat. 4 and 5 had significant/severe delay prior to the age of 21 months when they started having seizures).

All variants reported to date are truncating, affecting the last (sixth exon) and as a result may escape nonsense-mediated decay. Since TRIM8 homodimerizes via its (upstream) coiled-coil domain and its C-terminal domain is required for nuclear localization, a dominant-negative effect is postulated by the authors. Haploinsufficiency appears less likely.

A previously reported patient (from PMID: 27346735) as well as an individual reported by the Epi4K consortium (PMID: 23934111 - among the co-authors of the present study) are included in the table of this article.

As a result this gene can be upgraded to green.
Created: 17 Oct 2018, 2:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Intellectual disability; Seizures

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Please note new publication reporting 4 additional patients presenting with EE and de novo truncating mutations of TRIM8.
Created: 23 Oct 2018, 6 a.m.
Single family reported to date.
Created: 22 Aug 2018, 6:54 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
EE

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Early-onset epileptic encephalopathy (EOEE)
  • EE
  • Seizures
OMIM
606125
Clinvar variants
Variants in TRIM8
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to TRIM8.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to TRIM8.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Single family reported to date

3 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: trim8 has been classified as Green List (High Evidence).

3 Nov 2018, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: TRIM8 were changed from to Early-onset epileptic encephalopathy (EOEE); EE; Seizures

3 Nov 2018, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: TRIM8 were set to

3 Nov 2018, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: TRIM8 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: trim8 has been classified as Green List (High Evidence).

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to TRIM8. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

TRIM8 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

TRIM8 was created by Sarah Leigh