Ataxia and cerebellar anomalies - narrow panel
Gene: GLSRemoved the for-review tag as no changes are proposed for this gene at the moment.Created: 16 Mar 2022, 3:51 p.m. | Last Modified: 16 Mar 2022, 3:51 p.m.
Panel Version: 2.289
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: LiteratureCreated: 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
Tag for-review was removed from gene: GLS. Tag watchlist tag was added to gene: GLS.
Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Gene: gls has been classified as Amber List (Moderate Evidence).
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