Undiagnosed metabolic disordersGene: GLS
This gene is recently confirmed to be a cause for intellectual disability, ataxia, optic atrophy and biochemical evidence of very high glutamine levels without hyperammonaemia. A series of 3 patients is in press (NEJM) and presented at SSIEM 2018. One of the mechanisms of inheritance in some patients is a large tandem repeat which may coexist with a point mutation on the other allele. One patient has been found to be homozygous for the tandem repeat. Patients may be investigated for elevated glutamine with this panel and analysis of GLS should certainly now be included.
Created: 21 Dec 2018, 3:56 p.m.
Intellectual disability; Ataxia; Optic Atrophy
Mode of pathogenicity
Cannot find association for variants in this gene and monogenic disease. Not found in Orphanet, Gene2Phenotype or OMIM associated with a disease.
Created: 23 Feb 2017, 5:14 p.m.
Mode of inheritance
Construction of “Undiagnosed Metabolic Disorders” (UDM) panel • The 614 genes from the neurometabolic gene panel (PMID: 27604308) added • Green genes downloaded from V1 metabolic panels (Cerebral folate deficiency, Congenital disorders of glycosylation, Hyperammonaemia, Ketotic hypoglycaemia, Mitochondrial disorders, Mucopolysaccharideosis, Gaucher, Fabry, Peroxisomal disorders), sources replaced with "Expert review green", then loaded as a review onto UDM panel, resulting in 367 green genes and 333 red (therefore 86 new green genes included from the additional metabolic panels that weren't previously on the UDM panel) • Downloaded green genes from all panels. Removed genes from none V1 panels. Removed genes from the metabolic panels mentioned above. Compared the remaining genes with the red genes from UDM panel. Loaded as an "Expert review Amber" review to the overlapping genes, (the panel name where the genes came from was used as the phenotype) • Used variant information from PMID 27604308 to review the genes on this panel • Reviewed genes on UDM panel with genes from Emory "Inherited Metabolic Disorders: Sequencing Panel" and UKGTN “Inborn Errors of Metabolism 226 panel”, changing status where appropriate, added 14 UKGTN genes that had not be listed before • Review 10 red genes that had not previously been reviewed, 4/10 were reclassified as green • Review the remaining 145 red genes that had not previously been reviewed (shared between reviewers EM, RF, LD, AT, HB, ON & SL), resulting in 60 green, 11 amber, 70 red, 4 I don’t know reviews) • Reviewed genes from PMID: 24816252 as a publication to genes found in the Inborn error or metabolism Genes metabolomics GWAS paper (figure 5). 2 new genes added
GLS was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Red Model of inheritance for gene GLS was set to Unknown
GLS was created by sleigh
GLS was added to Undiagnosed metabolic disorderspanel. Sources: Literature