Originally published in The San Diego Union-Tribune by Bradley J. Fikes
More than 100 people gathered in San Diego on Sunday to discuss a rare disease that wasn’t even known to exist until three years ago.
Caused by mutations in a gene called DDX3X, the disease produces moderate to profound developmental disabilities. It’s associated with physical abnormalities in the brain. Some girls — nearly all those diagnosed are female — never learn to walk or talk.
While there are fewer than 120 known cases worldwide, the actual number of those affected could be far higher, according to researcher Elliott Sherr of UC San Francisco, considered the foremost authority on the disease.
In 2015, a study was published describing the disease, and its probable role in many unexplained cases of intellectual disability.
Parents and conference organizer DDX3X Foundation are raising money to support Sherr’s research. He’s trying to discover a drug to lessen disease symptoms and restore more normal brain activity.
Sherr and colleagues are painstakingly creating a mouse model of the disease to serve as a template to test potential drugs. If all goes well, he said at the conference, such a drug might be ready to show to drug companies by 2021.
Dr. Elliott Sherr of UC San Francisco describes to families of children with a genetic disorder how a single change in the building blocks of the protein DDX3X profoundly changes its function. Sher spoke in San Diego on Sunday, Nov. 5, 2017, at a conference held by the DDX3X Foundation.
Females are mostly affected because the mutant gene is on the X chromosome. Females have two X chromosomes, which provides some protection from mutations that affect only one chromosome. Males have only one X chromosome. Presumably, all but the mildest DDX3X mutations in males are lethal in the embryonic stage, Sherr said.
Dewey Marino of Point Loma said his 3-year-old daughter, Lucy, was diagnosed in 2014. Marino got involved with the foundation almost immediately. He arranged for the San Diego meeting to be held at the Handlery Hotel in Mission Valley.
Like the other parents at the conference, Marino and his wife, Tiffani Klug, got the diagnosis through whole exome sequencing. This method examines the small percentage of DNA that codes for proteins. In this disease, mutations in the gene result in defective production of a protein needed for normal neural development.
Lucy Marino, age 3, who has the DDX3X mutation. (Kate Auda.)
“We had a long journey trying to discover what was going on with Lucy,” Marino said. “She had global developmental delays. She had three strokes at the time of birth. There was no doctor who could diagnose her.”
Consultation at Rady Children’s Hospital in San Diego led to The Johns Hopkins Hospital in Baltimore, where they were urged to have whole exome sequencing performed on Lucy. A geneticist there also introduced the family to the DDX3X Foundation.
“Having a name for the disorder was very important for us to try to wrap our heads around what was really happening,” Marino said.
Also important was making connections with other parents.
“Seeing families that have progressed through adolescence with their girls helped us get an idea of where we were and what we should expect,” he said.
The foundation itself, as a new entity, has had to build an organization with worldwide reach from scratch. An application with the IRS to be recognized as a charitable entitled is pending. More information can be found at the foundation’s website at ddx3x.org.
(via The San Diego Union-Tribune)