Early onset or syndromic epilepsy
Gene: SLC12A5
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Comment on mode of inheritance: Changed Mode of Inheritance from 'BOTH monoallelic and bialleic, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' based on post-Webex review by Helen Lord.Created: 7 Sep 2019, 11:50 a.m. | Last Modified: 7 Sep 2019, 11:50 a.m.
Panel Version: 1.288
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
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
AR EIEE34 & AD generalised idiopathic epilepsy 14. AR EIEE34 - Stodberg et al, 2015 - 4 children from 2 unrelated families - hom/compound het variants in these families - in vitro studies showed that the nutations caused decreased membrane expression, impaired posttrnslational modification and a loss of transporter function resulting in impaired normal synaptic inhibition and promition if neuronal excitability. AD epilepsy - Kahle et al, 2014 - 380 epilepsy patients - 8 patients of French Canadian origin had two diff missense variants (5 - R952H & 3 - R1049C). In vitro expression studies showed that the variants impaired the functon of SLC12A5. Puskarjov et al, 2014 - 3 aff family members in an Australian family - R952H. In vitro studies also done - support pathogenicity.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, 616645; {Epilepsy, idiopathic generalized, susceptibility to}; 616685
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
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: 26333769Created: 21 Jan 2016, 1:12 p.m.
Gene: slc12a5 has been classified as Green List (High Evidence).
Phenotypes for gene: SLC12A5 were changed from epilepsy of infancy with migrating focal seizures (EIMFS) to epilepsy of infancy with migrating focal seizures (EIMFS); Epileptic encephalopathy, early infantile, 34, 616645; {Epilepsy, idiopathic generalized, susceptibility to, 14}, 616685
Publications for gene: SLC12A5 were set to PMID: 26333769; 24668262
Mode of inheritance for gene: SLC12A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mode of inheritance for gene: SLC12A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source Wessex and West Midlands GLH was added to SLC12A5.
Source NHS GMS was added to SLC12A5.
Ellen McDonagh: Comment on phenotypes: From PM
Victorian Clinical Genetics Services was added to SLC12A5. Panel: Genetic Epilepsy Syndromes
SLC12A5 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert Review
SLC12A5 was created by Sarah Leigh