Early onset or syndromic epilepsy

Gene: PEX1

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber.

Created: 25 Nov 2019, 8:56 p.m. | Last Modified: 25 Nov 2019, 8:56 p.m.

Panel Version: 1.448

PMID:16141001 (Rosewich et al 2005) studied 33 patients with PEX1 variants. Seizures are a feature in Table 3 for 6 patients.

Created: 21 Nov 2019, 3:31 p.m. | Last Modified: 21 Nov 2019, 3:31 p.m.

Panel Version: 1.418

PMID:15098231 (Poll-The BT et al 2004) surveyed 31 patients with a generalized peroxisomal disorder from 27 families. 7/31 patients (23%) developed seizures from 0 - 2.7 years. Most patients (60-70%) had variants in the PEX1 gene. Most frequent variants include G843D and frameshift c.2097insT.

Created: 21 Nov 2019, 3:26 p.m. | Last Modified: 21 Nov 2019, 3:26 p.m.

Panel Version: 1.417

PMID:15301838 (Michelakakis et al, 2004) decribe a female patient of healthy unrelated patients. Her diagnosis of Leber congenital amaurosis was subsequently demonstrated to be a PEX1 defect. Myoclonic seizures began age 2. The patient is heterozygous for G843D variant and an additional second variant that is not yet identified.

Created: 21 Nov 2019, 3:21 p.m. | Last Modified: 21 Nov 2019, 3:21 p.m.

Panel Version: 1.417

PMID:28432012 (Ge et al., 2017) report 2 Chinese newborns with Zellweger phenotypes and compound het variants in PEX1 (Arg577Thrfs*15 and Asn830Thrfx*61). Although the authors note that seizures are in the clinical spectrum of ZS patients, seizures were not reported for the Chinese newborns.

Created: 21 Nov 2019, 3:17 p.m. | Last Modified: 21 Nov 2019, 3:17 p.m.

Panel Version: 1.417

PMID:21844578 (Cho et al., 2011) report a Korean patient who was compound het for variants in the PEX1 gene (p.H678QfsX3 and p.R949W) inherited from the parents. He had typical features of ZS including seizures (starting 4 days old), dysmorphic face and a poor suck.

Created: 21 Nov 2019, 3:16 p.m. | Last Modified: 21 Nov 2019, 3:16 p.m.

Panel Version: 1.417

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: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

AR Perioxisome biogenesis disorder 1A and 1B and Heimler syndrome 1 (mild end of spectrum disorder - seizures not reported) . In the clinical feature section for both 1A and 1B I can' see any mention of seizures as part of the phenotype in these reported patients?

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
Heimler syndrome 1 234580; Peroxisome biogenesis disorder 1A (Zellweger) 214100; Peroxisome biogenesis disorder 1B (NALD/IRD) 601539

Publications

• 16141001

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Adrenoleukodystrophy. Seizures are a major feature of this phenotype (Genomics England clinical fellow Arianna Tucci). At least 5 variants reported in numerous unrelated cases.

Created: 7 Nov 2018, 5:01 p.m.

Comment on phenotypes: Adrenoleukodystrophy from Gen2Phen

Created: 7 Nov 2018, 4:59 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 18 Aug 2018, 10:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peroxisome biogenesis disorder 1A (Zellweger), MIM#214100

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