Intellectual disability - microarray and sequencing
Gene: GCSH
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.Created: 13 Mar 2023, 10:42 p.m. | Last Modified: 13 Mar 2023, 10:42 p.m.
Panel Version: 4.117
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.
The cases with the early-onset severe fatal glycine encephalopathy did not survive to develop intellectual disability/ developmental delay. The three patients with the attenuated phenotype had global developmental delay and limited communication skills while two of these cases had behavioural problems as well.
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, 10:35 p.m. | Last Modified: 13 Mar 2023, 10:35 p.m.
Panel Version: 4.114
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Publications
Comment on publications: PMID 25231368 & 29304759 report no GCSH variants in Glycine encephalopathy 605899Created: 5 Mar 2018, 12:27 p.m.
Associated with phenotype in OMIM and as a possible G2P association. At least 1 variant reported in 1 case.
Reported to be linked to isolated ID and ID associated disorders (PMID 26503795) and as candidate ID gene (PMID 24896178)Created: 5 Mar 2018, 12:12 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
GLYCINE ENCEPHALOPATHY
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 NHS GMS was added to 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).
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
Publications for gene: GCSH were set to 36190515
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
Publications for gene: GCSH were set to 36190515
Publications for gene: GCSH were set to 36190515
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 36190515
Publications for gene: GCSH were set to 36190515
Publications for gene: GCSH were set to 36190515
Publications for gene: GCSH were set to 36190515
Publications for gene: GCSH were set to
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
GCSH was added to Intellectual disabilitypanel. Source: Expert Review Red Model of inheritance for gene GCSH was set to BIALLELIC, autosomal or pseudoautosomal
GCSH was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen