Likely inborn error of metabolism - targeted testing not possible
Gene: GCSH
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 12:32 p.m. | Last Modified: 11 Oct 2023, 12:32 p.m.
Panel Version: 4.51
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.Created: 13 Mar 2023, 10:54 p.m. | Last Modified: 13 Mar 2023, 10:54 p.m.
Panel Version: 3.20
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.
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, 10:17 p.m. | Last Modified: 13 Mar 2023, 10:17 p.m.
Panel Version: 3.13
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Publications
Associated with Atypical glycine encephalopathy, Infantile glycine encephalopathy and Neonatal glycine encephalopathy in Orphanet, which are also linked to the AMT and GLDC genes which are both green in this panel and for which there are multiple cases from screens of patients which did not find variants within GCLC. PMID:12402263 describes a heterozygous variant identified in a patient with transient neonatal hyperglycinemia, which was also present in his mother and brother who had no family history of the disorder. Reported with a possible G2P association with MIM 605899. Not enough evidence at this time to be promoted.Created: 23 Feb 2017, 5:13 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Glycine encephalopathy 605899; Atypical glycine encephalopathy; Infantile glycine encephalopathy; Neonatal glycine encephalopathy; transient neonatal hyperglycinemia
Publications
Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. Only one variant reported in one caseCreated: 19 Jan 2017, 1:55 p.m.
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)
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Tag Q1_23_promote_green tag was added to gene: GCSH.
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Gene: gcsh has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: GCSH were changed from Glycine encephalopathy to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Publications for gene: GCSH were set to 27604308; 16450403; 36190515
Publications for gene: GCSH were set to 27604308; 16450403; 36190515
Publications for gene: GCSH were set to 27604308; 16450403; 36190515
Publications for gene: GCSH were set to 27604308; 16450403
Source NHS GMS was added to GCSH. Source London North GLH was added to GCSH.
Sarah Leigh: Associated with phenotype in O
gene: GCSH was added gene: GCSH was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: GCSH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GCSH were set to 27604308; 16450403 Phenotypes for gene: GCSH were set to Glycine encephalopathy