Epileptic encephalopathy

Gene: SLC12A5

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• Stodberg et al (2015) Nat. Commun. 6:8038 doi: 10.1038/ncomms9038

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• Stodberg et al (2015) Nat. Commun. 6:8038 doi: 10.1038/ncomms9038

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• Stodberg et al (2015) Nat. Commun. 6:8038 doi: 10.1038/ncomms9038

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• Stodberg et al (2015) Nat. Commun. 6:8038 doi: 10.1038/ncomms9038

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

Comment on mode of inheritance: Both applies to information from reviewers, G2P and OMIM, and publications.

Created: 29 Jan 2016, 5:10 p.m.

PMID: 25839329 - Two families, each with two children with EIMFS with similar presentation, were investigated. Missense mutations within the SLC12A5 gene were reported in all four children, with a recessive mode of inheritance. The children from Family A were compound heterozygotes for missense mutations c.1277T>C (L426P) and c.1652G>A (G551D). The affected patients from Family B were homozygous for the missense variant c.932T>A (L311H). Parents were heterozygous carriers. No potential pathogenic variants were found in known EIMFS or EIEE genes in the families. Postulated mechanism from in vitro/in vivo studies is through reduced surface expression, impairing normal synaptic inhibition and promoting neuronal excitability.

PMID: 24668262 - 378 patients with seizure disorders were analyzed and 11 rare variants in SLC12A% were identified. In one family, rs142740233 NM_020708.4:c.2855G>A missense variant (causing Arg>His at position 952 in KCC2b and 975 in KCC2a) was found. The KCC2b isoform of the variant (named KCC2-R952H) was investigated further and was shown to result in reduced cell surface expression.

Created: 21 Jan 2016, 1:51 p.m.

Comment on phenotypes: From PMID: 26333769

Created: 21 Jan 2016, 1:12 p.m.