Selected Grantee Publications
- Clear All
- 2 results found
- Aquatic Vertebrate Models
- Pediatrics
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).
Loss of Gap Junction Delta-2 (GJD2) Gene Orthologs Leads to Refractive Error in Zebrafish
Quint et al., Communications Biology. 2021.
https://pubmed.ncbi.nlm.nih.gov/34083742/
Myopia is the most common developmental disorder of juvenile eyes. Although little is known about the functional role of GJD2 in refractive error development, the authors find that depletion of gjd2a (Cx35.5) or gjd2b (Cx35.1) orthologs in zebrafish cause changes in eye biometry and refractive status. Their immunohistological and scRNA sequencing studies show that Cx35.5 (gjd2a) is a retinal connexin; its depletion leads to hyperopia and electrophysiological retina changes. They found a lenticular role; lack of Cx35.1 (gjd2b) led to a nuclear cataract that triggered axial elongation. The results provide functional evidence of a link between gjd2 and refractive error. Supported by ORIP (R24OD026591), NIGMS, and NINDS.