Selected Grantee Publications

De Novo and Inherited Variants in DDX39B Cause a Novel Neurodevelopmental Syndrome

Booth et al., Brain. 2025.

https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awaf035/8004980?login=true

DDX39B is a core component of the TRanscription-EXport (TREX) super protein complex. Recent studies have highlighted the important role of TREX subunits in neurodevelopmental disorders. Researchers describe a cohort of six individuals (male and female) from five families with disease-causing de novo missense variants or inherited splice-altering variants in DDX39B. Three individuals in the cohort are affected by mild to severe developmental delay, hypotonia, history of epilepsy or seizure, short stature, skeletal abnormalities, variable dysmorphic features, and microcephaly. Using a combination of patient genomic and transcriptomic data, in silico modeling, in vitro assays, and in vivo Drosophila and zebrafish models, this study implicates disruption of DDX39B in a novel neurodevelopmental disorder called TREX-complex-related neurodevelopmental syndrome. Supported by ORIP (U54OD030165).