Early onset or syndromic epilepsy

Gene: TRAPPC12

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

Green List (high evidence)

Comment on list classification: With addition of the recently reported case, there are now at least 3 unrelated patients with epilepsy and biallelic variants in this gene (PMIDs: 28777934 and 32369837).

This now reaches threshold for inclusion as diagnostic-grade, and therefore TRAPPC12 can be promoted to Green at the next GMS panel update (added 'for-review' tag)

Created: 20 Jan 2021, 5:24 p.m. | Last Modified: 20 Jan 2021, 5:24 p.m.

Panel Version: 2.259

- PMID: 32369837 (2020) - Two further unrelated patients with severe neurodevelopmental delay and brain atrophy, and different homozygous variants in this gene. One individual also presented microcephaly and epilepsy (generalized tonic-clonic convulsions by this first year of life). The second individual did display EEG abnormalities but without seizures.

Created: 20 Jan 2021, 5:20 p.m. | Last Modified: 20 Jan 2021, 5:20 p.m.

Panel Version: 2.258

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 32369837

Green List (high evidence)

Limited evidence: two of the three cases in PMID 28777934 had seizures.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, 617669

Publications

• 28777934

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber:

Created: 15 Aug 2019, 8:11 a.m. | Last Modified: 15 Aug 2019, 8:11 a.m.

Panel Version: 1.223

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: Alison Callaway and John Taylor. 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: Kept rating as Amber: 2 families only in PMID:28777934. Seizures are a phenotype in 2/3 of the patients (one patient from each family).

Created: 8 Nov 2018, 9:38 a.m. | Last Modified: 4 Jul 2019, 10:42 a.m.

Panel Version: 1.109

In 3 patients from 2 unrelated families with early-onset progressive encephalopathy with brain atrophy and spasticity (MIM:617669), Milev et al. (2017, PMID:28777934) identified homozygous or compound heterozygous mutations in the TRAPPC12 gene. Epilepsy is reported in 2/3 patients (the patient from family I, and one of the sisters from family II; the other sister showed monoclonic jerks only).

Created: 8 Nov 2018, 9:37 a.m. | Last Modified: 4 Jul 2019, 10:41 a.m.

Panel Version: 1.109

I don't know

Only two families reported in the literature.

Created: 22 Aug 2018, 6:40 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM#617669

Publications

• 28777934

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