Epilepsies are a biologically complex group of disorders comprising many discrete genetic entities, and the majority of recurrent seizure syndromes remain unexplained. Most, if not all, epileptic disorders can be traced to abnormalities of brain structure or chemistry that alter the electrical activity of nerve cell networks. The children in this study have autistic traits, also thought to be caused by disrupted nerve cell networks.
The finding, which is published in the March 30th issue of the New England Journal of Medicine, describes the newly discovered disorder called cortical dysplasia-focal epilepsy syndrome (CDFE) in a group of closely related Old Order Amish children from Pennsylvania.
All affected children had relatively normal development until the onset of frequent intractable seizures in early childhood. Thereafter, they developed language regression and additional features of autism, possibly implicating this gene as a cause of autism in the general population. Physicians at the CSC isolated DNA from four of the affected children and their six parents and, in collaboration with TGen, identified a mutation in the gene that codes for a protein called CASPR2.
New GeneChip technologies for scanning the human genetic blueprint are powerful tools for rapidly identifying causes of disorders such as epilepsy in carefully selected families.
"The ability to rapidly decipher the genetic underpinnings of brain disorders through genetic technologies will allow the medical community to better understand disorders such as autism and epilepsy, and this understanding is the first step in developing effective treatments" said Dr. Dietrich Stephan, Director of the Neurogenomics Division at TGen, Scientific Director of the TGen/Southwest Autism Research and Resource Center’s (SARRC) autism research program, and a senior author on the study.
The protein has a well-known role in maintaining physical contacts between neurons and neighboring glial cells in the mature nervous system, but this is the first evidence that CASPR2 is also important for early human brain development.
According to Dr. Erik Puffenberger, laboratory director at the CSC, "We were able to unequivocally map the disease gene to chromosome 7 and identify a pathogenic sequence variant in the gene CNTNAP2, which codes for the CASPR2 protein. Although these patients were from an isolated population, we anticipate that CASPR2 mutations will be found in children from other populations with mental retardation, seizures, and autism."
"Previous studies on CASPR2 in isolated cell cultures and genetic ’knockout’ mice did not predict its fundamental role in human brain development or cortical electrical activity. The present findings are compelling evidence for such roles, and open new directions for epilepsy and autism research beyond the index population," said Dr. Kevin Strauss, a pediatrician at the CSC.
According to Dr. Holmes Morton, co-founder and medical director of the CSC, "The identification of the mutation in CASPR2 in our Amish patients has already allowed us to recognize affected newborns before they become symptomatic. Our hope is that early treatment and prevention of prolonged seizures in these infants will lessen the effects of the disorder upon the lives of children and their families."
Amy Erickson | EurekAlert!
Nanocages in the lab and in the computer: how DNA-based dendrimers transport nanoparticles
19.10.2018 | University of Vienna
Less animal experiments on the horizon: Multi-organ chip awarded
19.10.2018 | Fraunhofer-Institut für Werkstoff- und Strahltechnik IWS
Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.
Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...
Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles
Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...
When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.
We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...
Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...
Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...
17.10.2018 | Event News
16.10.2018 | Event News
02.10.2018 | Event News
22.10.2018 | Physics and Astronomy
19.10.2018 | Life Sciences
19.10.2018 | Physics and Astronomy