Early onset or syndromic epilepsy

Gene: SLC25A22

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
Epileptic encephalopathy, early infantile, 609304

Publications

• 19780765
• 24596948
• 15592994

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 3

Publications

• Molinari et al (2005) Am J Hum Genet 76: 334_339

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 3

Publications

• Molinari et al (2005) Am J Hum Genet 76: 334_339

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 3

Publications

• Molinari et al (2005) Am J Hum Genet 76: 334_339

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 3

Publications

• Molinari et al (2005) Am J Hum Genet 76: 334 339

Mode of pathogenicity
loss-of-function (truncating variants and curated list of variants)

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

Comment when marking as ready: All reviewers agree this gene should be green and would report variants within this gene as part of their current diagnostic practice. Probable DD gene. Mutation consequence summary from G2P: all missense/in frame.

Created: 29 Jan 2016, 2:44 p.m.

Comment on mode of inheritance: Confirmed on G2P and OMIM.

Created: 29 Jan 2016, 2:30 p.m.