- An international team of researchers has identified eight genes linked to developmental and epileptic encephalopathy (DEE) .
What is DEE?
DEE is a catch-all term scientists use to refer to conditions where individuals have both an intellectual disability and epilepsy as a result of some combination of epileptic and developmental encephalopathy .
Epilepsy is a neurological disorder that affects the electrical activity of the brain, causing those afflicted to experience seizures .
Encephalopathy is a disease that also affects the brain . Epileptic encephalopathies are a severe subset of epilepsy associated with cognitive and behavioral impairment resulting from the seizures that the affected individual’s experience .
In developmental encephalopathy, genetic or environmental factors can lead to impairments that occur prior to seizures affecting the individual .
The genetic disorders that cause these two forms of epilepsy may cause a specific form of encephalopathy in one individual but may lead to a different form of encephalopathy in another individual .
What was the goal of the study?
Researchers conducted Whole-Genome Sequencing (WGS) on 197 patients from the Canadian Epilepsy Network (CENet) . All of the patients had a variety of DEE that was unexplained by clinical evaluation and were experiencing treatment-resistant seizures .
The study aimed to identify de novo mutations (DNMs) in the patient’s genomes. De novo mutations (DNMs) are genetic variations that arise for the first time in a given family member, usually due to a mutation inherited from one of their parents . After identifying the DNMs, the study identified links between the DNMs and the genes associated with these mutations to ultimately develop biomarkers for improved clinical diagnosis of DEE .
How did they find the genes?
The study analyzed the 197 sequenced genomes of DEE patients, and looked at the regions of every individual’s DNA responsible for encoding proteins, which are called coding regions . The team then searched the coding regions for 3 forms of DNMs, including single-nucleotide variations (SNVs), small insertions and deletions (indels), and copy-number variations (CNVs).
Single-nucleotide variations occur when a single nucleotide is altered in a gene’s sequence. Small insertions and deletions occur when nucleotides are either inserted in or deleted from the coding region . Copy-number variants is a catch-all term that includes variations (insertions, deletions, and duplications) of an individual’s DNA segment .
Finally, the researchers identified a subset of genes that corresponded to mutations that were being highly expressed in the DEE patients and not the healthy patients, and therefore were actively impacting their health . The team discovered eight genes that are believed to be causally linked to DEE. These genes may serve as the foundation for the development of a diagnostic tool that would better detect the disease in a clinical setting .
Thought Question for Students
How can the identification of genes with de novo mutations lead to improved health outcomes for future patients?
- High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. (2017, November 02). Retrieved January 09, 2018, from http://www.sciencedirect.com/science/article/pii/S0002929717303774?via%3Dihub
- What is Epilepsy. (n.d.). Retrieved March 7, 2018, from https://www.cureepilepsy.org/about-epilepsy/what-is-epilepsy
- Definition of de novo mutation – NCI Dictionary of Cancer Terms. (n.d.). Retrieved January 09, 2018, from https://www.cancer.gov/publications/dictionaries/genetics-dictionary?cdrid=460142
- Indel. (n.d.). Retrieved January 09, 2018, from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/indel
- Definition of CNV – NCI Dictionary of Cancer Terms. (n.d.). Retrieved January 16, 2018, from https://www.cancer.gov/publications/dictionaries/genetics-dictionary?CdrID=600384