Early onset or syndromic epilepsy
Gene: PEX1
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
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
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 Gen2PhenCreated: 7 Nov 2018, 4:59 p.m.
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
Gene: pex1 has been classified as Amber List (Moderate Evidence).
Publications for gene: PEX1 were set to 12402331; 26387595; 9398847
Source Wessex and West Midlands GLH was added to PEX1.
Source NHS GMS was added to PEX1.
Zornitza Stark: Seizures are part of the pheno
Gene: pex1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: PEX1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX1 were set to
Phenotypes for gene: PEX1 were changed from Peroxisome biogenesis disorder 1A (Zellweger) 214100; Peroxisome biogenesis disorder 1B (NALD/IRD) 601539 to Peroxisome biogenesis disorder 1A (Zellweger) 214100; Peroxisome biogenesis disorder 1B (NALD/IRD) 601539; Adrenoleukodystrophy
Gene: pex1 has been classified as Green List (High Evidence).
Phenotypes for gene: PEX1 were set to Peroxisome biogenesis disorder 1A (Zellweger) 214100; Peroxisome biogenesis disorder 1B (NALD/IRD) 601539
Expert Review Amber was added to PEX1. Panel: Genetic Epilepsy Syndromes
PEX1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PEX1 was created by Sarah Leigh