Ataxia and cerebellar anomalies - narrow panel
STR: GLS_GCAGRCh37 Position: 191745599-191745646
GRCh38 Position: 190880873-190880920
Repeated Sequence: GCA
Normal Number of Repeats: < 50
Pathogenic Number of Repeats: = or > 400
GLS (glutaminase)
EnsemblGeneIds (GRCh38): ENSG00000115419
EnsemblGeneIds (GRCh37): ENSG00000115419
OMIM: 138280, Gene2Phenotype
GLS is in 0 panels
1 review
Arina Puzriakova (Genomics England Curator)
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 this 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Red but will raise the STR for validation with the Rare Disease team.Created: 19 Jan 2021, 11:42 a.m. | Last Modified: 19 Jan 2021, 11:42 a.m.
Panel Version: 2.37
GLS is associated with relevant phenotypes 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, 11:36 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
- Name
- GLS_GCA
- Chromosome
- 2
- GRCh37 Coordinates
- 191745599-191745646
- GRCh38 Coordinates
- 190880873-190880920
- Repeated Sequence
- GCA
- Normal Number of Repeats: <
- 50
- Pathogenic Number of Repeats: = or >
- 400
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Red
- Literature
- Phenotypes
-
- Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
- Tags
- OMIM
- 138280
- Clinvar variants
- Variants in GLS
- Penetrance
- None
- Publications
History Filter Activity
Removed Tag
Eleanor Williams (Genomics England Curator)Tag for-review was removed from STR: GLS_GCA.
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for STR: GLS_GCA 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
Entity classified by Genomics England curator
Arina Puzriakova (Genomics England Curator)Str: gls_gca has been classified as Red List (Low Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Arina Puzriakova (Genomics England Curator)STR: GLS_GCA was added STR: GLS_GCA was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature STR, NGS Not Validated, for-review tags were added to STR: GLS_GCA. Mode of inheritance for STR: GLS_GCA was set to BIALLELIC, autosomal or pseudoautosomal Publications for STR: GLS_GCA were set to 30970188 Phenotypes for STR: GLS_GCA 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 STR: GLS_GCA was set to GREEN