Global Developmental Delay, Progressive Ataxia, and Elevated Glutamine (GLS)
| Dred_ID | RD00041 |
| OMIM ID | 618412 |
| Disease name | Global Developmental Delay, Progressive Ataxia, and Elevated Glutamine |
| Alternative names | GDPAG |
| Category | Genetic diseases |
| Phenotype | OMIM: Patients with global developmental delay, progressive ataxia, and elevated glutamine (GDPAG) present in early childhood with delay of both gross and fine motor skills and delayed speech. Ataxia develops by mid- to late childhood, necessitating use of a walker or wheelchair. Plasma glutamine is persistently elevated by a factor of 2.5 despite normal plasma ammonia levels. Residual glutaminase (GLS) activity can be detected in fibroblasts and lymphocytes. One or both alleles of the GLS gene carry an expanded GCA trinucleotide repeat in the 5-prime untranslated region (UTR); the repeat expansion may be found in compound heterozygosity with another GLS mutation. Three patients have been reported (summary by van Kuilenburg et al., 2019). (618412) (Updated 29-Dec-2021). MalaCards based summary: Global Developmental Delay, Progressive Ataxia, and Elevated Glutamine, also known as glutaminase deficiency with impaired intellectual development and progressive ataxia, is related to infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development. An important gene associated with Global Developmental Delay, Progressive Ataxia, and Elevated Glutamine is GLS (Glutaminase). Affiliated tissues include brain, and related phenotypes are global developmental delay and delayed speech and language development. |
| Miscellaneouse | Based on a report of 3 unrelated patients (last curated april 2019) |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | autosomal recessive |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | GLS |
| Alias symbols | GAC; GAM; KGA; GLS1; AAD20; DEE71; GDPAG; CASGID; EIEE71 |
| Gene name | glutaminase |
| Gene map locus | 2q32.2; chr2:190,880,821-190,965,552(+) |
| Ensembl Gene ID | ENSG00000115419 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene encodes the K-type mitochondrial glutaminase. The encoded protein is an phosphate-activated amidohydrolase that catalyzes the hydrolysis of glutamine to glutamate and ammonia. This protein is primarily expressed in the brain and kidney plays an essential role in generating energy for metabolism, synthesizing the brain neurotransmitter glutamate and maintaining acid-base balance in the kidney. Alternate splicing results in multiple transcript variants. |
| Repeat unit | GCA |
| Normal repeat copies | 8-16 |
| Pathogenic repeat copies | ≥680 |
| Gene | GLS |
| Repeat location | 5' UTR |
| Chromosome locus | chr2:190880874-190880901 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| PMID | 30970188 |
| Authors | André B P van Kuilenburg, Maja Tarailo-Graovac, Phillip A Richmond, Britt I Drögemöller, Mahmoud A Pouladi, René Leen, Koroboshka Brand-Arzamendi, Doreen Dobritzsch, et al |
| Title | Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS |
| Journal | The new england journal o f medicine |
| Year | 2019 |