A homozygous TARS2 variant is a novel cause of syndromic neonatal diabetes
Authors' conclusion
Our findings establish the homozygous p.(Arg327Gln) TARS2 variant as a novel cause of syndromic neonatal diabetes and uncover a role for TARS2 in pancreatic β-cells.
Study context
- Population
- Individuals with neonatal diabetes plus epilepsy and/or developmental delay of unknown genetic cause; replication in individuals with diabetes diagnosed aged ≤1 year without known genetic cause
- Participants
- 27 vs 123
- Exposure
- Genome sequencing vs Replication studies
- Genome sequencingn = 27
- Replication studiesn = 123
- Outcome
- Identification of novel genetic causes of neonatal diabetes with neurological features
Methodological detailsgenome sequencing, replication cohort with targeted next-generation sequencing
- Genome sequencing
- Replication cohort with targeted next-generation sequencing
Main finding
As reported in the abstract
Homozygous TARS2 p.(Arg327Gln) missense variant
- Discovery cohort: individuals sharing rare homozygous TARS2 p.(Arg327Gln) variant, all diagnosed with diabetes in first week of life
- 3
- Replication cohort: individual with same homozygous variant, diabetes diagnosed at 1 year
- 1
- Neurological features: epilepsy only
- 1
- Neurological features: developmental delay only
- 1
- Neurological features: both epilepsy and developmental delay
- 2
Observational data: associations, not effects.
Further findings
Proposed mechanism
- Current evidence suggests the variant disrupts TARS2's regulation of the mTORC1 pathway, essential for β-cells
Original publication
A homozygous TARS2 variant is a novel cause of syndromic neonatal diabetes. Diabet Med. Published 7 November 2024. doi:10.
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