Early onset or syndromic epilepsy
Gene: SLC6A19
As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Epilepsy is not a key feature. Demoted from Green to Red.Created: 25 Nov 2019, 9:09 p.m. | Last Modified: 25 Nov 2019, 9:09 p.m.
Panel Version: 1.460
PMID:20399395 (Cheon et al 2010) report a Korean boy age 8 years and 5 months with Hartnup disorder. He had seizures, ADHD and mental retardation. Genetic analysis revealed novel compound het variants in SLC6A19: p.Thr596fsX73 and p.Ser303Leu.Created: 21 Nov 2019, 4:52 p.m. | Last Modified: 21 Nov 2019, 4:52 p.m.
Panel Version: 1.423
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: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
AR Hartnup disorder, AD hyperglycinuria and AR & DR digenic Iminoglycinuria. Hartnup disorder - seizures are mentioned as a feature in OMIM but can only see one listed case where the patient had epilepsy. Google search state variable features but not found any specific mentions of epilepsy/seizures. Has a variable phenotype as symptoms triggered by sunlight, fever, drugs or emotional/physical stress - symptoms occur sporadic and are due to a deficiency of the niacin derived enzyme co-factors. Dietary factors also influence presentation as a high protein diet is good (often asymptomatic). Can be diagnosed by a urine/blood tests. Don't add to panel.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
Hartnup disorder,234500; Hyperglycinuria,138500; Iminoglycinuria, digenic,242600
Publications
Seizures listed as a clinical feature of Hartnup disorder 234500, considered to be appropriate by Dr Arianna Tucci (Neurology, UCL). Associated with phenotypes in OMIM, not in G2P / DD. At least 6 variants reported in 8 cases of Hartnup disorder 234500Created: 6 Feb 2017, 10:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hartnup disorder 234500
Publications
Gene: slc6a19 has been classified as Red List (Low Evidence).
Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, 234500
Publications for gene: SLC6A19 were set to
Source Wessex and West Midlands GLH was added to SLC6A19.
Source NHS GMS was added to SLC6A19.
Sarah Leigh: Seizures listed as a clinical
SLC6A19 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review,Literature,Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green
SLC6A19 was created by Sarah Leigh