Early onset or syndromic epilepsy

Gene: NUBPL

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: Alison Callaway and John Taylor. 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

better tested through the mito panel. Mitochondrial disorders can associated with seizures, but the evidence is not specifically implicated. There are reports of disease-causing variants being associated with complex I deficiency.

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 I deficiency, nuclear type 21, 618242

Publications

• 20818383

Comment when marking as ready: Sufficient cases associating NUBPL with Mitochondrial complex I deficiency but not sufficient cases with epilepsy/seizure phenotype to rate this gene green on this panel.

Created: 14 Nov 2018, 2 p.m.

Comment on list classification: Keeping Amber as only 1 confirmed case of patient with epilepsy

Created: 14 Nov 2018, 1:57 p.m.

Associated with Mitochondrial complex I deficiency in OMIM and Gene2Phenotype. Sufficient cases associating NUBPL with Mitochondrial complex I deficiency but not sufficient cases with epilepsy/seizure phenotype. The patient described in PMID: 20818383 (Calvo et al. (2010)) had staring spells, possibly indicating absence seizures from age 2 but the EEG was normal. He was treated with sodium valproate and no definite seizures have occurred subsequently.

PMID: 23553477 Kevelam et al. (2013) report 6 patients from 5 unrelated families with complex I deficiency and a characteristic leukoencephalopathic pattern on brain MRI. The patients had biallelic mutations in the NUBPL gene. However only 1 showed epilepsy.

Created: 14 Nov 2018, 1:55 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 11:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, MIM#252010

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