Our understanding of the DDX3X mutations’ effects began in November 2014, when a very human connection between friends encouraged research that had not been done before. Out of that research came a clue, that DDX3X gene mutations could be linked to intellectual disabilities that can range from mild to profound, abnormalities of the brain, seizures, or autism. The patient pool quickly grew from 1, to 10, to dozens as families that never knew the name of the disorder affecting their children suddenly had a term, and a support system. In August of 2015, a paper was published in The American Journal of Human Genetics titled Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling-August 2015. A team of doctors from all over the world studied 38 female individuals and discovered that mutations in DDX3X are a common cause of unexplained intellectual disability.
Researchers across the globe are now looking at the DDX3X mutations and their effects. Our mission is to help families and researchers move forward.
Do you think your daughter could have the DDX3X gene mutation?
The following are common symptoms:
- Intellectual disabilities
- Low weight
- Low muscle tone
- Movement disorders
- Skin abnormalities
- Hearing loss
DDX3X gene mutations can be found using a test called Whole Exome Sequencing (WES). WES is a test that sequences the protein-coding regions of the 19,000 genes in an individual. Alterations in these regions of DNA are believed to underlie about 85-90% of genetic conditions. This test has been very helpful in the diagnosis of rare disorders, and led to the discovery of the DDX3X condition when several laboratories performing this test for patients with intellectual disabilities found a number of them all had changes in the DDX3X gene. Together, they collected their information and performed additional studies that further characterized the condition and led to the American Journal of Human Genetics publication in August 2015.
Nowadays, DDX3X mutations are a known cause of intellectual disability and will be detected on WES. This explains why so many more children are suddenly being identified with the condition. Whole exome sequencing is becoming more readily available, affordable, and common for the diagnosis of conditions believed to have a genetic basis.
GeneDx, a Maryland-based genetic testing company, was one of the first laboratories to identify the DDX3X gene and the association between alterations in this gene and intellectual disabilities. It is one of several clinical laboratories that does WES. Testing by WES must be requested by a doctor and the results sent to a medical facility. Families interested in WES should discuss that option with their doctor, who may recommend genetic counseling and a Genetics evaluation to determine if WES is the appropriate diagnostic test to pursue.
A series of talks at a DDX3X Family day with speakers including geneticists and genetic counselors