Early onset or syndromic epilepsy

Gene: TMEM70

I don't know

AR mitochondrial complex V deficiency - on OMIM it says that seizures are uncommon.

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 V (ATP synthase) deficiency nuclear type 2, 614052

Publications

• 25326274
• 21147908

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. Insufficient seizure evidence. Demoted from Green to Amber.

Created: 25 Nov 2019, 9:11 p.m. | Last Modified: 25 Nov 2019, 9:11 p.m.

Panel Version: 1.461

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

Comment on list classification: Updated rating from Amber to Green: Green review, and Confirmed DD-G2P gene for Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 which can present with seizures. Seizures reported in 3 unrelated patients from the literature (2 in PMID:18953340 and 1 in PMID:21147908) so just sufficient cases for Green rating.

Created: 8 Nov 2018, 9:46 a.m.

In 6 patients from 4 unrelated consanguineous Arab-Muslim families with MC5DN2, Spiegel et al. (2011, PMID:21147908) identified 4 different homozygous mutations in the TMEM70 gene. Patient IV-1 developed generalised seizures at age 13.

Created: 8 Nov 2018, 9:42 a.m.

In affected individuals from 6 Romani families with neonatal mitochondrial encephalocardiomyopathy associated with complex V (ATP synthase) deficiency (MC5DN2; 614052), Cizkova et al. (2008, PMID:18953340) identified a homozygous splicing variant in the TMEM70 gene (c.317-2A-G). The same homozygous mutation was identified in 23 additional patients. Patient 1 had Status epilepticus, and Patient 5 developed epileptic spasms at the age of 3 years (Table 1 and text).

Created: 8 Nov 2018, 9:42 a.m.

Green List (high evidence)

Seizures are part of the phenotype in this mitochondrial disorder.

Created: 22 Aug 2018, 5:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM#614052

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