Gene/phenotype/disorder of interest
RUNX1T1 (OMIM 133435)
Abstract
RUNX1T1, previously known as ETO, MTG8, or CBFA2T1, encodes a highly conserved and ubiquitously expressed transcriptional corepressor that functions as part of multiple transcriptional repressor complexes. It has been studied extensively in the context of leukemia, where its fusion with the myeloid transcription factor RUNX1 (AML1) gives rise to the leukemogenic RUNX1::RUNX1T1 fusion protein.
RUNX1T1 interacts with several corepressors, including histone deacetylases (HDACs) and components of distinct HDAC-containing repressor complexes, highlighting its central role in epigenetic regulation and chromatin remodeling.
Although germline pathogenic variants in RUNX1T1 have not yet been definitively linked to a human genetic disorder, the gene is highly expressed in the cerebral cortex and cerebellum. Emerging evidence suggests that RUNX1T1 is a strong candidate neurodevelopmental disease gene.
We are establishing an international cohort of individuals with loss-of-function variants in RUNX1T1, as well as individuals with chromosomal deletions encompassing the gene. Through this collaborative effort, we aim to collect and analyze detailed clinical, genomic, and phenotypic data to better define the associated syndrome, characterize its facial gestalt, investigate the underlying disease mechanisms, and explore genotype–phenotype correlations.
Coordinating clinicians
- Nathalie Vanden Eynde: Nathalie.vandeneynde@lns.etat.lu
- Guillaume Jouret: Guillaume.jouret@lns.etat.lu
Institution
National Center of Genetics, Laboratoire National de Santé, Luxembourg
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples: N
- Resampling of patients: N
- Linked to a translational/basic research project? N