Targeted gene(s)/phenotype under study
By trio-based exome sequencing, we identified a missense variant (c.542C>A:p.S181Y) in DLX1, in a female patient with severe intellectual disability, microcephaly, structural brain anomalies, epilepsy and behavioural anomalies such Rett-like features. Through collaborations, we have collected additional cases with similar phenotype, harbouring either missense or nonsense variants in DLX1
DLX1 encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. It plays a regulatory role in the development of the ventral forebrain, specifically promoting the synthesis, synaptogenesis and dendritogenesis of GABAergic interneurons. Moreover, DLX1 has been suggested as a candidate gene for Autism spectrum disorder.
We are planning to generate patients’ iPSC-derived neurons and investigate the underlying neurodevelopmental processes by an integrated approach, involving high resolution imaging techniques, electrophysiology and transcriptomics.
In summary there is a growing body of evidence to consider DLX1 as a novel neurodevelopmental disorder gene. We look for further patients with DLX1 variants displaying similar clinical features.
Coordinating clinicians /researchers
- Andrea Accogli
- Valeria Capra
Specific requirements beyond clinical data and genotype data sharing
- Re-analysis of DNA samples : No
- Resampling of patients : No
- Linked to a translational/basic research project? Yes