Early onset or syndromic epilepsy
Gene: GCSH
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 11:59 a.m. | Last Modified: 11 Oct 2023, 11:59 a.m.
Panel Version: 4.110
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on list classification: This gene should be rated GREEN as there are five unrelated cases identified with biallelic variants in GCSH and reported with seizures/ epilepsy as part of the phenotype. one case was reported in PMID:1671321 and four in PMID:36190515 (three with severe neonatal/ infantile phenotype and one with attenuated phenotype).Created: 13 Mar 2023, 10:12 p.m. | Last Modified: 13 Mar 2023, 10:12 p.m.
Panel Version: 3.108
PMID:36190515 reported six unrelated individuals with biallelic variants in GCSH. They presented with a broad clinical spectrum with three cases with an early-onset severe fatal glycine encephalopathy and the other three cases displaying an attenuated phenotype of developmental delay, behavioural problems, epilepsy and variable movement problems and they had long-term survival. The three early-onset and fatal cases displayed compound heterozygous variants, while the cases with attenuated phenotype harboured homozygous variants.
All three individuals with the early-onset severe fatal glycine encephalopathy had epilepsy/ seizures as part of the presenting phenotypes. Only patient (patient 6) from the three cases with the attenuated phenotype had left-sided partial seizures, while other two had no seizures/ epilepsy.
Functional studies in patient's fibroblasts, molecular modeling, expression analysis in GCSH knockdown COS7 cells and yeast, and in vitro protein studies demonstrated that most variants identified in this cohort produced a hypomorphic effect on both protein lipoylation and glycine metabolism, causing combined deficiency, whereas some missense variants affected primarily one function only.
This gene has also been associated with Glycine encephalopathy in both OMIM and Gene2Phenotype.Created: 13 Mar 2023, 10:02 p.m. | Last Modified: 13 Mar 2023, 10:14 p.m.
Panel Version: 3.108
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Publications
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: Red.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
AR ? Glycine encephalopathy - neonatal and infantile forms assocaited with seizures but not the mild or late-onset forms. With neonatal form may not survive to point of developing seizures.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
?Glycine encephalopathy, 605899
Publications
Comment on list classification: Based on reviewers' comments.Created: 11 Dec 2018, 1:20 p.m.
Single case reported, insufficient evidence.Created: 14 Aug 2018, 12:54 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Glycine encephalopathy, MIM#605899
Publications
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423; Glycine encephalopathy; Transient neonatal hyperglycinemia
Tag Q1_23_promote_green was removed from gene: GCSH.
Source Expert Review Green was added to GCSH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q1_23_promote_green tag was added to gene: GCSH.
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: GCSH were changed from to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Publications for gene: GCSH were set to
Mode of inheritance for gene: GCSH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: GCSH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: GCSH was changed from to BIALLELIC, autosomal or pseudoautosomal
Source Wessex and West Midlands GLH was added to GCSH.
Source NHS GMS was added to GCSH.
Zornitza Stark: Single case reported, insuffic
Gene: gcsh has been classified as Red List (Low Evidence).
Expert Review Amber was added to GCSH. Panel: Genetic Epilepsy Syndromes
GCSH was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
GCSH was created by Sarah Leigh