Our ultimate goal over the coming years is to accelerate brain function in individuals affected by DDX3X through advances in gene therapy and pharmaceuticals.
The DDX3X Foundation understands that a strong, collaborative, patient-focused research-network is critical to cure DDX3X syndrome. In late 2014 the first patient with a DDX3X gene mutation was identified in the United States and by yearend eight girls had been diagnosed. Since that time, we have formalized our patient-led collaborative research network in partnership with clinicians and scientists. Born in 2015 and made official with the IRS as a 501(c)3 nonprofit in December of 2017, the DDX3X Foundation’s ambition has been to accelerate brain function in individuals affected by DDX3X gene mutations through the creation of a patient-led research-network focused on advancing gene therapy and pharmaceuticals. Since 2015, we have facilitated the acceleration of research on DDX3X gene mutations by increasing the network of researchers from one to twenty and research papers from one to more than thirty. We have accomplished this work through an annual research conferences that bring together patients, families, and scientists, a basic patient-registry, formation of a scientific advisory board, and countless hours of networking with researchers from around the world. Researchers represented at our DDX3X conferences have included:
- Sanchita Bhatnagar, PhD, Assistant Professor, Biochemistry and Molecular Genetics, University of Virginia School of Medicine
- Karlla Brigatti, MS, Genetic Counselor, Clinic for Special Children
- Randy J. Chandler, PhD, Staff Scientist, National Human Genome Research Institute at the National Institutes of Health (NIH)
- Silvia DeRubeis, PhD, Assistant Professor, Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai
- Maria Escolar, MD, Director of the Program for the Study of Neurodevelopment in Rare Disorders, Children’s Hospital of Pittsburgh of UPMC
- Kevin Francis, PhD, Assistant Professor, Department of Pediatrics at the Sanford School of Medicine at the University of South Dakota
- Dorothy Grice, MD, Professor, Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai
- Robert Jinks, PhD, Professor of Neuroscience, Biological Foundations of Behavior program at Franklin & Marshall College
- Bethany Johnson-Kerner, MD, Ph.D, Research Fellow, Univerity of California, San Francisco (UCSF)
- Jane Juusola, PhD, Director of the Whole Sequencing Program, GeneDX
- Kevin Strauss, MD, Medical Director, Clinic for Special Children
- Linda Richards, PhD, Professor of Neuroscience and Deputy Director, Queensland Brain Institute at The University of Queensland (Australia)
- Elliott Sherr, MD, PhD, Professor in Neurology and Pediatrics, Institute of Human Genetics and the Weill Institute of Neurosciences at the University of California, San Francisco (UCSF)
- Debra L. Silver, PhD, Associate Professor, Departments of Molecular Genetics and Microbiology, Cell Biology, and Neurobiology and Director of Graduate Studies at Duke Developmental and Stem Cell Biology
Momentum to unlock the potential of individuals with DDX3X syndrome continues to build as the rosters of researchers and diagnosed families grows each day.
Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling
Intellectual disability (ID) affects approximately 1%–3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence...
Phenotypic expansion in DDX3X – a common cause of intellectual disability in females
De novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID), one of the most common causes of ID, in females. Forty-seven patients (44 females, 3 males) have been described. We identified 29 additional...
Pathogenic DDX3X mutations impair RNA metabolism and neurogenesis during fetal cortical development
De novo germline mutations in the RNA helicase DDX3X account for 1-3% of unexplained intellectual disability (ID) cases in females, and are associated with autism, brain malformations, and epilepsy. Yet, the developmental...
De novo DDX3X missense variants in males appear viable and contribute to syndromic intellectual disability
DDX3X (Xp11.4) encodes a DEAD‐box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in DDX3X have been shown to cause X‐linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated...
A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features
Intellectual disability (ID) is a common condition with a population prevalence frequency of 1–3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among the more than 500 genes...
Identification of Intellectual Disability Genes in Female Patients with a Skewed X‐Inactivation Pattern
Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X‐linked ID (XLID) studies focused on males because of the hemizygous state of their X chromosome. Carrier...
Ongoing published research on DDX3X
Research on DDX3X gene functionality and mutations has accelerated drastically over the last years. A listing of all the DDX3X papers published to date can be found here:
DR. SHERR AT UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
As a pediatric neurologist, Elliott Sherr, MD, PhD has spent a significant portion of his career studying the brains of children with malformations. When a beautiful young girl presented in his clinic with dysgenesis of the corpus callosum, he went above and beyond to help her family find answers—which ended up being a mutation of her DDX3X gene. Three years later he is going above and beyond for all children with DDX3X mutations. Individuals with DDX3X are included in his lab’s Brain Development Research Program which seeks to better understand the function of the DDX3X gene.
NATURAL HISTORY STUDY, CHILDREN'S HOSPITAL OF PITTSBURGH OF UPMC
Board certified in neurodevelopmental disabilities, Maria Luisa Escolar, MD, MS established the Program for the Study of Neurodevelopment in Rare Disorders (NDRD) to help children and their families understand the impact of rare neurological diseases on child development. In late 2017, Dr. Escolar began seeing individuals with DDX3X gene mutations in her clinic. Rare diseases, especially newly discovered disorders like DDX3X gene mutations, are poorly understood. As more and more patients participant in Dr. Escolar’s natural history study—consisting of several evaluations, an MRI, and an exam—their journey adds to a collective body of knowledge to help families meet the challenges of day-to-day life with DDX3X and science advance research on rare condition.
RARE DISEASE PROGRAM, SEAVER AUTISM CENTER AT MOUNT SINAI
The Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai is tracking the natural history of the five single-gene causes of autism, including DDX3X. The program seeks to identify and develop specific biomarkers that can serve to monitor treatment response; develop models to generate and test treatments; and test potential new treatments. To date, over 150 families have enrolled in the Rare Disease Program.
SKIN SAMPLE STUDY, THE CORIELL INSTITUTE
The study of skin biopsy samples from individuals with DDX3X gene mutations could allow researchers to improve the function of the mutated DDX3X gene. Parents interested in providing a skin sample of their child, as well as their own, to be stored at the Coriell Institute should contact Tara Schmidlen ([email protected] or 856-757-4822). Tara is the genetic counselor and coordinator who works closely with a host of patient registries and individual families and can help work out the logistics of providing a sample. Be sure to specify that your child has a DDX3X gene mutation. The Coriell Institute is a large public biobank with a long and successful experience banking patient samples for a host of different genetic disorders. Stored samples will allow researchers from around the world to access them for free if they’re contributing to the bank (or the researcher who has contributed gives them access).
Natural History Study
Contact program coordinator Brie Yanniello ([email protected] or 412-692-6350) to schedule an appointment at Children’s Hospital of Pittsburgh of UPMC
Contact clinical research coordinator Lara Tang ([email protected] or 212-241-2993) to schedule an appointment at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai
Skin Sample Study
Contact Tara Schmidlen ([email protected] or 856-757-4822) to provide a skin sample of your child, as well as your own, to be stored at the Coriell Institute.
There is power in numbers. Join our patient registry to add your child to the growing number of children with DDX3X.