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Early onset or syndromic epilepsy v4.112 | GCSH | Arina Puzriakova 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v4.111 | GCSH | Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GCSH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v4.110 | GCSH | Arina Puzriakova reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v4.109 | GCSH |
Arina Puzriakova Source Expert Review Green was added to GCSH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Early onset or syndromic epilepsy v3.108 | GCSH | Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GCSH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.108 | GCSH |
Achchuthan Shanmugasundram changed review comment from: 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.;; to: 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. |
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Early onset or syndromic epilepsy v3.108 | GCSH | Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.108 | GCSH | Achchuthan Shanmugasundram Added comment: 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). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.108 | GCSH | Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.107 | GCSH |
Achchuthan Shanmugasundram changed review comment from: 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.; to: 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.; |
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Early onset or syndromic epilepsy v3.107 | GCSH | Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.106 | GCSH | Achchuthan Shanmugasundram Publications for gene: GCSH were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.105 | GCSH | Achchuthan Shanmugasundram Mode of inheritance for gene: GCSH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.105 | GCSH | Achchuthan Shanmugasundram Mode of inheritance for gene: GCSH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.105 | GCSH | Achchuthan Shanmugasundram Mode of inheritance for gene: GCSH was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v3.104 | GCSH | Achchuthan Shanmugasundram reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36190515; Phenotypes: ?Glycine encephalopathy, OMIM:605899, Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.191 | GCSH | Rebecca Foulger Source Wessex and West Midlands GLH was added to GCSH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.190 | GCSH | Rebecca Foulger Source NHS GMS was added to GCSH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.189 | GCSH | Rebecca Foulger reviewed gene: GCSH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.188 | GCSH | Tracy Lester reviewed gene: GCSH: Rating: RED; Mode of pathogenicity: ; Publications: 1671321; Phenotypes: ?Glycine encephalopathy, 605899 ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1532 | GCSH | Sarah Leigh Classified gene: GCSH as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1532 | GCSH | Sarah Leigh Added comment: Comment on list classification: Based on reviewers' comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.1532 | GCSH | Sarah Leigh Gene: gcsh has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | GCSH | Zornitza Stark reviewed gene: GCSH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | GCSH | Sarah Leigh Added gene to panel |