De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity

From a patient’s genetic finding to a disease model and towards future therapies. We are proud to share a new study published in Nature Communications, in which the Czech Centre for Phenogenomics (CCP) played a key role in uncovering the mechanism of a rare neurodevelopmental disorder associated with EHMT2 variants.

The study, led by Stanislav Kmoch from the 1. lékařská fakulta UK, connected clinical genetics, genomics, molecular and structural biology with experimental disease modelling. At CCP, the team of Radislav Sedlacek created and characterised a genetically engineered mouse model carrying an EHMT2 variant corresponding to the variant identified in a patient. The model provides an important tool for understanding how the mutation contributes to disease and for future research into potential therapeutic approaches.

This work is a great example of what can be achieved when patients, clinicians, geneticists and research infrastructures work together, connecting an individual genetic finding with biological mechanisms and experimental models.

Original publication:
De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity, Nature Communications, 2026. PubMed: PMID 42386776. doi: 10.1038/s41467-026-74987-w. PMID: 42386776; PMCID: PMC13462943. Full article