The 2 organizations will use whole-genome sequencing and clinical characterization to investigate the genetic causes of CP.
The Shriners Hospital for Children (SHC) and Jackson Laboratory (JAX) have announced a collaboration to research the genetic factors of cerebral palsy (CP).1 Together, SHC and JAX will apply clinical characterization and whole genome sequencing to a de-identified database of 500 children with CP treated at SHC in what will be, to date, the largest-scale investigation of this kind into children with CP.
“Despite discovering CP in the 19th century, little progress has been made in understanding its causes,” said lead investigator Peter Robinson, MD, MSc, professor, computational biology, Jackson Laboratory, in a statement. “This is an excellent opportunity to gain a better understanding of the genetic variants and molecular pathways that underlie CP or contribute to increased susceptibility to it. We hope that this knowledge will translate to improved care in the coming years.”
Kamran Shazand, MD, PhD, director, Genomics Institutes Labs, Shriners Hospital for Children, and adjunct professor, University of South Florida, and his team will perform whole genome sequencing of the DNA samples. Jon R. Davids, MD, assistant chief, orthopedic surgery, Shriners Hospitals for Children, and Ben Ali Chair in Pediatric Orthopedics, University California at Davis, will lead the detailed clinical and phenotypic characterization of children with CP. Robinson will lead the computational analysis of the large dataset.
“The partnership with Peter Robinson and JAX lab provides the opportunity to learn more about the genetic causes of CP, which will certainly have an impact on clinical decision-making in the future, and perhaps someday facilitate the development of novel treatment paradigms that will minimize the musculoskeletal manifestations of this condition,” Davids added to the statement.
The collaboration between the institutes also represents a unique opportunity to combine clinical and research resources. Robinson, in addition to working in genomic analysis, also develops tools to facilitate work and analysis with clinical data such as that contained in electronic medical records. These tools will be used to bridge together the genomic and clinical characterization work that will be performed in the 2 arms of the research and allow the researchers to associate genetic variations with disease traits and patient diagnoses with precision.
Charles Lee, PhD, FACMG, director and professor, Jackson Laboratory, added to the statement that “understanding the genetic mechanisms behind CP could result in an entirely new way of looking at this disorder, providing hope and potential new treatment options for the many children and families affected by CP.”
CP, the most common motor disability in childhood, affects approximately 1 in every 500 children. Despite its prevalence, the cause in most cases is unclear and no diagnostic tests or effective therapies exist. A recent study largely funded by the National Institute of Neurological Disorders and Stroke (NINDS) confirmed that around 14% of cases may be linked to a patient’s genes and suggest that many of those genes control how brain circuits are wired during early development.2 Results also showed that 2% of cases are linked to recessive versions of genes.
Investigators in that study also found that patients with CP had higher levels of potentially harmful de novo mutations than their parents, many of which appeared to be concentrated in genes that are highly sensitive to the slightest changes in the DNA letter code. They then estimated that 11.9% of the cases could be explained by damaging de novo mutations. Notably, this was found to be especially true for those who were idiopathic, which represented 62.8% of the cases in the study.
Specifically, 6 of the 8 genes that had 2 or more de novo mutations control the wiring of neural circuits during early development. These genes are known to be involved in the protein scaffolds that line the perimeters of neural circuits or in the growth and extension of neurons as they wire up.
“Cerebral palsy is one of neurology’s oldest unresolved mysteries. The results from this study show how advances in genomic research provide scientists with the hard evidence they need to unravel the causes behind this and other debilitating neurological disorders,” Jim Koenig, PhD, program director, NINDS, said in a statement.
NeurologyLive recently spoke with Bhooma Aravamuthan, MD, DPhil, assistant professor of pediatric neurology, Department of Neurology, Washington University in St Louis, about some of the challenges in CP diagnosis for episode 33 of the Mind Moments podcast. She shared her findings from a recent survey of child neurologists and neurodevelopmentalists inquiring about their roles in the diagnosis of the disease, which has several mimics and can present difficulties for community neurologists.