Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: GLS

Amber List (moderate evidence)

GLS (glutaminase)
EnsemblGeneIds (GRCh38): ENSG00000115419
EnsemblGeneIds (GRCh37): ENSG00000115419
OMIM: 138280, Gene2Phenotype
GLS is in 8 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Progressive ataxia is the main feature of the disease presentation (childhood-onset), and there are sufficient unrelated cases for inclusion as diagnostic-grade.

However, detection of the 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Amber but will raise the STR for validation with the Rare Disease team.
Created: 19 Jan 2021, noon | Last Modified: 19 Jan 2021, noon
Panel Version: 2.39
GLS is associated with relevant phenotype in OMIM, but currently is not in Gene2Phenoype.
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- PMID: 30970188 (2019) - Three unrelated cases who presented with an early-onset global developmental delay, progressive ataxia, and elevated levels of glutamine (MIM# 618412). One patient also showed cerebellar atrophy.

All 3 individuals harboured a large trinucleotide (GCA) repeat expansion in the 5' UTR (length: 680-1,500-copy repeats). The repeat expansion was found in homozygosity in 1 case, and occurred in compound heterozygosity with an SNV in the other two cases (missense and frameshift variant, respectively). Functional analysis showed the repeat expansion results in reduced expression and glutaminase deficiency.
Sources: Literature
Created: 19 Jan 2021, 11:58 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
  • Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733
Tags
STR for-review
OMIM
138280
Clinvar variants
Variants in GLS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

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

19 Jan 2021, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: GLS was added gene: GLS was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature STR, for-review tags were added to gene: GLS. Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLS were set to 30970188 Phenotypes for gene: GLS were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 Review for gene: GLS was set to GREEN