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Genetic epilepsy syndromes

Gene: GSS

Amber List (moderate evidence)

GSS (glutathione synthetase)
EnsemblGeneIds (GRCh38): ENSG00000100983
EnsemblGeneIds (GRCh37): ENSG00000100983
OMIM: 601002, Gene2Phenotype
GSS is in 7 panels

3 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, 8:53 p.m. | Last Modified: 25 Nov 2019, 8:53 p.m.
Panel Version: 1.444
PMID:26669244 (Gunduz et al., 2016) report 4 patients with GS deficiency. Case I and Case IV had seizures noted together with homozygous variants (splicing variant in I and p.R125H in IV): Table 1.
Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.
Panel Version: 1.415
Seizures are recorded in OMIM Clinical synopsis for MIM:266130 based on Marstein et al., 1976 (no PubMed).
Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.
Panel Version: 1.415
PMID:15990954 (Njallson et al 2005) summarise the phenotypes of patients with glutathione synthetase deficiency, but don't mention seizures or epilepsy (as noted in review by Tracy Lester).
Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.
Panel Version: 1.415
PMID:11445798 (Ristoff et al,. 2001) examined 28 patients with Glutathione synthetase deficiency (GSSD). Diagnosis was based on metabolic tests. 16/28 had neurological symptoms such as seizures/psychomotor retardation. In 16 patients with severe GS deficiency, 7 had seizures.
Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.
Panel Version: 1.415
PMID:26984560 (Atwal et al. 2016) present a 19 year old female with Glutathione synthetase deficiency (GSSD). She was diagnosed with a mild seizure disorder age 10, and treated with the antiepileptic lamotrigine, which was discontinued once she was seizure free for 5 years. The authors note it is possible her seizures were unrelated to the underlying GSSD.
Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.
Panel Version: 1.415
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

AR gluathione synthetase deficiency - in severe form as massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia and CNS damage. Njallson et al, 2005 - clinical phenotype evaluated in 41 patients from 33 families - no mention of specific phenotypes with regards to epilepsy. 1 patient in OMIM mentioned as having seizures - Marstein et al, 1976.
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
Glutathione synthetase deficiency,266130; Hemolytic anemia due to glutathione synthetase deficiency,231900

Publications

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on'treatable' tag due to information from PMID:15990954 vitamins C and E to boost their antioxidant levels, and bicarbonate to correct metabolic acidosis.
Created: 20 Mar 2017, 11:09 a.m.
Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.
Created: 20 Mar 2017, 11:08 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glutathione synthetase deficiency 266130; Hemolytic anemia due to glutathione synthetase deficiency 231900

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review
Phenotypes
  • Glutathione synthetase deficiency 266130
  • Hemolytic anemia due to glutathione synthetase deficiency 231900
OMIM
601002
Clinvar variants
Variants in GSS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Nov 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

21 Nov 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: GSS were set to 26984560

21 Nov 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: GSS were set to

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to GSS.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to GSS.

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Sarah Leigh: Inclusion of this as a green g

4 Apr 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

GSS was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert Review

4 Apr 2018, Gel status: 4

Created

Sarah Leigh (Genomics England Curator)

GSS was created by Sarah Leigh