Early onset or syndromic epilepsy

Gene: PET100

Green List (high evidence)

Mi/AR mitochondrial complex IV deficiency - Associatred with Leigh syndrome - may be more appropriate on mitochondrial panel.

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
Mitochondrial complex IV deficiency,220110

Publications

• 24462369

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: Green review, and Green rating agreed by Sarah Leigh. Seizures are a recognised phenotype of patients with Mitochondrial complex IV deficiency, which can be caused by variants in multiple genes, including PET100. 2 different PET100 variants reported so far in the literature (including a founder variant in Lebanese patients) in >3 unrelated individuals with seizures as a prominent phenotype (PMIDs24462369 and 23829769).

Created: 12 Nov 2018, 5:01 p.m.

Added 'founder effect' tag based on PMID:24462369 who identified a founder variant in patients of Lebanese descent.

Created: 12 Nov 2018, 4:52 p.m.

PMID:23829769 report a female patient born to British Pakistani parents with seizures beginning at 48 hours old. She died age 55 hours. She had a pathogenic homozygous nonsense variant in the PET100 gene (c.142C>T, p.Gln48*).

Created: 12 Nov 2018, 4:23 p.m.

PMID:24462369 (Lim et al) studied ten individuals with IV-deficient Leigh Syndrome. All ten affected individuals were of Lebanese descent, and were homozygous for a founder c.3G>C variant predicted to abolish the first methionine residue. Seizures were a prominent feature, and reported in 8 individuals from 6 families not known to be related.

Created: 12 Nov 2018, 4:15 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 18 Aug 2018, 10:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex IV deficiency, MIM#220110

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