Early onset or syndromic epilepsy
Gene: GCH1
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. Better tested through the metabolic panel. Demoted from Green to Amber.Created: 25 Nov 2019, 8:51 p.m. | Last Modified: 25 Nov 2019, 8:51 p.m.
Panel Version: 1.441
Additional evidence for seizures being part of the metabolic disorder comes from PMID:31202265 (Dayasiri et al, 2019) who report a S. Asian child with AR GTPCH (GCH1) deficiency, diagnosed from metabolic testing and family consanguinity. Features included recurrent seizures since 3 months old.Created: 21 Nov 2019, 12:12 p.m. | Last Modified: 21 Nov 2019, 12:12 p.m.
Panel Version: 1.409
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
Epilepsy is not one of the cardinal features. AR BH4-deficient hyperphenylalaninemia B - Horvath et al, 2008 - table 1 - seizures reported in GTPCH deficiency with HPA, classic phenotype: AR.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
Dystonia, DOPA-responsive, with or without hyperphenylalaninemia 128230; Hyperphenylalaninemia, BH4-deficient, B 233910
Publications
Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease associationCreated: 20 Nov 2018, 4:54 p.m.
Comment on publications: Added publications to support upgrading of the gene to GreenCreated: 20 Nov 2018, 4:52 p.m.
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panelCreated: 20 Nov 2018, 4:28 p.m.
Seizures are part of the phenotype of this metabolic disorder.Created: 14 Aug 2018, 12:48 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hyperphenylalaninemia, BH4-deficient, B, MIM#233910
Variants in this GENE are reported as part of current diagnostic practice
Gene: gch1 has been classified as Amber List (Moderate Evidence).
Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309; 31202265
Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309
Publications for gene: GCH1 were set to 7869202; 17407085; 12552057
Source Wessex and West Midlands GLH was added to GCH1.
Source NHS GMS was added to GCH1.
Zornitza Stark: Seizures are part of the pheno
Gene: gch1 has been classified as Green List (High Evidence).
Gene: gch1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: GCH1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCH1 were set to
Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, 233910; seizures
Expert Review Amber was added to GCH1. Panel: Genetic Epilepsy Syndromes
GCH1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
GCH1 was created by Sarah Leigh