Activity
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| Neonatal diabetes v5.9 | TARS2 | Ida Ertmanska edited their review of gene: TARS2: Changed phenotypes to: Combined oxidative phosphorylation deficiency 21, OMIM:615918, combined oxidative phosphorylation defect type 21, MONDO:0014398 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.9 | TARS2 | Ida Ertmanska Phenotypes for gene: TARS2 were changed from Neonatal diabetes; developmental delay; epilepsy to Combined oxidative phosphorylation deficiency 21, OMIM:615918; combined oxidative phosphorylation defect type 21, MONDO:0014398 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.8 | TARS2 | Ida Ertmanska Publications for gene: TARS2 were set to PMID: 39509107 and PMID: 37454282 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.7 | TARS2 | Ida Ertmanska Classified gene: TARS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.7 | TARS2 | Ida Ertmanska Gene: tars2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.6 | TARS2 |
Ida Ertmanska commented on gene: TARS2: Comment on list classification: Out of more than 30 individuals reported in literature with biallelic TARS2 variants and Combined oxidative phosphorylation deficiency 21, only 4 patients presented with the additional phenotype of neonatal diabetes. 4/4 of those patients were homozygous for the same missense variant p.(Arg327Gln) - 3 families had a shared haplotype (PMID:39509107, Donis et al., 2025). An additional patient with TARS2-related COXPD-21 and diabetes was reported in PMID: 37454282 Accogli et al., 2023 - age of onset unknown. Based on the available evidence, this gene should be rated Amber for Neonatal diabetes until more evidence emerges. Importantly, ID/DD and axial hypotonia are the main features reported in COXPD-21 patients (92% and 85% of individuals respectively - PMID: 39509107). TARS2 is already rated Green / tagged for promotion on other panels in PanelApp which cover the most common symptoms, including: Intellectual disability; Childhood onset dystonia, chorea or related movement disorder; Mitochondrial disorders . |
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| Neonatal diabetes v5.6 | TARS2 | Ida Ertmanska reviewed gene: TARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24827421, 34508595, 37454282, 39394138, 39509107; Phenotypes: Combined oxidative phosphorylation deficiency 21, OMIM:615918; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.6 | TARS2 |
Anna-Marie Johnson gene: TARS2 was added gene: TARS2 was added to Neonatal diabetes. Sources: Literature Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TARS2 were set to PMID: 39509107 and PMID: 37454282 Phenotypes for gene: TARS2 were set to Neonatal diabetes; developmental delay; epilepsy Penetrance for gene: TARS2 were set to Complete Mode of pathogenicity for gene: TARS2 was set to Other Review for gene: TARS2 was set to GREEN Added comment: Donis et al 2024 (PMID: 39509107) performed WGS on 27 neonatal diabetes patients who also had epilepsy and/or developmental delay. 3 individuals were found to be homozygous for a TARS2 missense variant, c.980G>A, p.(Arg327Gln). A replication cohort identified 1 additional individual who is also homozygous for this variant. An additional patient with diabetes (age of diagnosis not provided) and COXPD-21 related features has been reported with compound heterozygous TARS2 variants (Accogli et al 2023, PMID: 37454282). Biallelic TARS2 variants cause Combined Oxidative Phosphorylation Deficiency-21(COXPD-21, 21;OMIM: 615918) and neonatal diabetes is a reported feature of this disorder. Evidence shows that the p.(Arg327Gln) variant disrupts TARS2's regulation of the mTORC1 pathway which is essential for pancreatic beta-cells. Sources: Literature |
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