Early onset or syndromic epilepsy

Gene: SLC25A1

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

Green List (high evidence)

AR Combined D-2 and L-2 hydroxyglutaric acidurea. Seizures are a feature. Muntau et al, 2000 - 3 patients including 2 sibs - all had seizures and other features. All died in early childhood - transmission patterns suggestive of AR - don't think genetic testing done. Nota et al, 2013, 12 patients from unrelated families of Arabic, European or Latin American descent - all had seizures, missense, nonsense and fs -hom/compound het in all patients. Edvardson et al, 2013 - 18 month old girl - developed epilepsy - compound het mutation. Pop et al, 2018 - overview. To date 16 mutations reported (26 patients) - 75% missense, seizures seen clinically in 20 patients - functional assay done to look at expression studies in the missense variants - variants did seem to lead to impaiment of CIC function, in addtion those with less impaired function seemed to have a milder presentation.

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
?Myasthenic syndrome, congenital, 23, presynaptic 618197; Combined D-2- and L-2-hydroxyglutaric aciduria, 615182

Publications

• 29226520
• 23561848

Green List (high evidence)

Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.

Created: 20 Mar 2017, 11:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined D-2- and L-2-hydroxyglutaric aciduria 615182