The DDX3X syndrome is caused by mutations in the human DDX3X gene. It was discovered merely 5 years ago, but has quickly drawn a tremendous amount of research interest as one of the most common genetic diseases that lead to intellectual disability in females. A private foundation, called the DDX3X Foundation, was established a few years ago in downtown Wilmington DE to coordinate the research and patent care for this devastating disease (https://ddx3x.org). While nearly all studies to date focused on the brain and psychological problems caused by these mutations, we noticed that many symptoms displayed by these patients, including facial and skull malformations, congenital heart diseases, and pigment defects, are likely caused by deficiencies in a special type of stem cells called the neural crest cells. Using developing frog embryos as a model, my lab showed for the first time that the DDX3X gene is essential for neural crest development; we went on to demonstrate that DDX3X functions in neural crest development by controlling several other genes. Consistent with our findings, human mutations in nearly all of these downstream genes have been linked to highly similar neural crest and brain defects in the past few years. The goal of this R01 grant is to further explore the connections between DDX3X and these downstream genes, and understand how the human mutations result in the symptoms. We hope that these studies can lead to novel strategies to diagnose and prevent these devastating birth defects.
UDaily Article - Where Trouble Starts