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Genetic epilepsy syndromes

Gene: GCH1

Amber List (moderate evidence)

GCH1 (GTP cyclohydrolase 1)
EnsemblGeneIds (GRCh38): ENSG00000131979
EnsemblGeneIds (GRCh37): ENSG00000131979
OMIM: 600225, Gene2Phenotype
GCH1 is in 16 panels

4 reviews

Rebecca Foulger (Genomics England curator)

I don't know

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

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

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

Louise Daugherty (Genomics England Curator)

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Created: 20 Nov 2018, 4:54 p.m.
Comment on publications: Added publications to support upgrading of the gene to Green
Created: 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 panel
Created: 20 Nov 2018, 4:28 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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

History Filter Activity

25 Nov 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: gch1 has been classified as Amber List (Moderate Evidence).

21 Nov 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309; 31202265

21 Nov 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309

21 Nov 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: GCH1 were set to 7869202; 17407085; 12552057

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to GCH1.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to GCH1.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are part of the pheno

20 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gch1 has been classified as Green List (High Evidence).

20 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gch1 has been classified as Green List (High Evidence).

20 Nov 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: GCH1 was changed from to BIALLELIC, autosomal or pseudoautosomal

20 Nov 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: GCH1 were set to

20 Nov 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, 233910; seizures

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to GCH1. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

GCH1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

GCH1 was created by Sarah Leigh