Glossary of SCN2A-Related Terms
Learning how to talk and read about SCN2A and SCN2A-related disorders may require some new vocabulary.
This glossary is a collection of terms that will be helpful to understand when learning about SCN2A-related disorders. It will unlock the scientific language used in research papers, scientific presentations, and conversations with clinicians and peers.
Action Potential: A rapid rise and subsequent fall in voltage or membrane potential across a cellular membrane, typically observed in neurons and muscle cells, essential for the transmission of nerve impulses.
Amino Acid: An amino acid is the fundamental molecule that serves as the building block for proteins. There are 20 different amino acids. SCN2A is composed of 2005 amino acids.
Autism Spectrum Disorder (ASD): A developmental disorder that affects communication and behavior. Some individuals with SCN2A mutations may exhibit features of ASD.
Autosomal Dominant: A pattern of inheritance where only one copy of a mutated gene is sufficient to cause a disorder. Many SCN2A-related disorders follow an autosomal dominant inheritance pattern.
Channelopathy: A disease caused by disturbed function of ion channel subunits or the proteins that regulate them. SCN2A-related disorders are a type of channelopathy.
Codon: A codon is a DNA or RNA sequence of three nucleotides (a trinucleotide) that forms a unit of genomic information encoding a particular amino acid or signaling the termination of protein synthesis (stop signals). There are 64 different codons: 61 specify amino acids and 3 are used as stop signals.
Comorbidity: Distinct health conditions that are present at the same time. They may exist together for many reasons, including shared causes and risk factors.
CRISPR/Cas9: A genome editing technology that can be used to make precise changes in DNA. This technology is being explored for potential therapeutic interventions for SCN2A-related disorders.
De Novo Mutation: A genetic mutation that is present for the first time in one family member as a result of a variant in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself.
Developmental Delay: When a child does not reach their developmental milestones at the expected times. This can occur in various domains such as motor, language, social, or cognitive skills.
Electroencephalogram (EEG): A test that detects electrical activity in the brain using small, flat metal discs (electrodes) attached to the scalp. EEGs are often used to diagnose epilepsy and other brain disorders.
Electrophysiological Recording: The measurement of electrical activity in neurons. This technique is used to study the effects of SCN2A mutations on neuronal function.
Electrophysiology: The study of the electrical properties of biological cells and tissues. Electrophysiological techniques are used to measure the function of SCN2A sodium channels.
Epilepsy: A neurological disorder characterized by recurrent seizures. Mutations in SCN2A are associated with certain types of epilepsy.
Epileptic Encephalopathy: A severe form of epilepsy that affects brain function and development. SCN2A mutations are a known cause of epileptic encephalopathy.
Excitatory Synapses: Connections between neurons where the release of neurotransmitters leads to an increase in the likelihood of the receiving neuron firing an action potential. SCN2A mutations can influence these synapses.
Frameshift Mutation: A frameshift mutation in a gene refers to the insertion or deletion of nucleotide bases in numbers that are not multiples of three. If a mutation disrupts this normal reading frame, then the entire gene sequence following the mutation will be incorrectly read. This can result in the addition of the wrong amino acids to the protein and/or the creation of a codon that stops the protein from growing longer.
Functional Assay: An experimental procedure used to measure the activity of a protein. Functional assays are used to determine the impact of SCN2A mutations on sodium channel activity.
Gain-of-Function Mutation: A type of mutation in which the altered gene product possesses a new molecular function or a new pattern of gene expression. Some SCN2A mutations lead to excessive sodium influx in neurons, resulting in hyperexcitability.
Gene Therapy: A technique that modifies a person's genes to treat or cure disease. Gene therapy is a potential approach for treating SCN2A-related disorders.
Genetic Testing: A medical test that identifies changes in chromosomes, genes, or proteins. Genetic testing for SCN2A mutations can help diagnose related disorders.
Genotype: The genetic constitution of an individual organism. For SCN2A, this refers to the specific mutation(s) in the SCN2A gene.
Haploinsufficiency: A condition in which a single functional copy of a gene is insufficient to maintain normal function. This can occur in SCN2A-related disorders when one copy of the gene has a loss-of-function mutation.
Heterozygous Mutation: A mutation in which only one of the two copies of a gene is altered. SCN2A-related disorders typically arise from heterozygous mutations.
Hyperexcitability: An increased responsiveness of neurons to stimuli, which can result in excessive neuronal firing and is often associated with seizures. This can be a consequence of gain-of-function mutations in SCN2A.
In Vitro: Studies or experiments conducted outside of a living organism, typically in a lab setting such as in a petri dish or test tube. In vitro studies are often used to investigate SCN2A function.
In Vivo: Studies or experiments conducted within a living organism. In vivo studies help understand the impact of SCN2A mutations in a whole organism context.
Inhibitory Interneurons: A type of neuron that reduces the activity of other neurons. Dysfunction in SCN2A can affect these neurons, potentially leading to an imbalance between excitatory and inhibitory signals in the brain.
Intellectual Disability: A term used when a person has certain limitations in cognitive functioning and skills, including communication, social, and self-care skills. This can be a feature of SCN2A-related disorders.
Ion Channelopathy: Diseases caused by dysfunctional ion channels, which in the context of SCN2A, often lead to neurological symptoms such as epilepsy or developmental disorders.
Loss-of-Function Mutation: A mutation that results in the gene product having less or no function. Certain SCN2A mutations reduce the activity of the sodium channel, leading to reduced neuronal excitability.
Missense Mutation: A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. Many SCN2A mutations are missense mutations that affect sodium channel function.
Molecular Dynamics Simulation: A computer simulation technique used to study the physical movements of atoms and molecules. It can be used to model the impact of SCN2A mutations on sodium channel structure and function.
Mosaicism: the presence of cells in a person that have a different genome from the body’s other cells. This difference could be due to a specific genomic variant, for example, or the addition or loss of a chromosome. The condition can stem from a genetic error that occurs after fertilization of an egg, during very early embryo development, or it could occur later in development. Mosaicism can affect any type of cell and does not always cause disease.
Mutation: A change in the DNA sequence of a gene. Mutations in the SCN2A gene can lead to various neurological disorders.
N-of-1: single subject clinical trials that consider an individual patient as the sole unit of observation in a study investigating the efficacy or side-effect profiles of different interventions. The ultimate goal of an n-of-1 trial is to determine the optimal or best intervention for an individual patient using objective data-driven criteria.
Nav1.2: The protein produced by the SCN2A gene, also referred to as a sodium channel subunit, which plays a key role in the excitability of neurons.
Neurodevelopmental Disorder: A group of conditions with onset in the developmental period, often before a child enters grade school, characterized by developmental deficits that produce impairments of personal, social, academic, or occupational functioning.
Neurogenetics: The study of the genetic basis of the development and function of the nervous system. SCN2A research is a significant aspect of neurogenetics.
Neuronal Excitability: The ability of neurons to respond to stimuli and convert them into neural impulses. SCN2A mutations can alter neuronal excitability.
Neurotransmitter: A chemical substance that transmits signals across a synapse from one neuron to another. Sodium channel function, regulated by SCN2A, is crucial for neurotransmitter release.
Nonsense Mutation: A nonsense mutation occurs in DNA when a sequence change gives rise to a stop codon rather than a codon specifying an amino acid. The presence of the new stop codon results in the production of a shortened protein that is likely non-functional.
Nucleotide: A nucleotide is the basic building block of nucleic acids (RNA and DNA). The bases used in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). In RNA, the base uracil (U) takes the place of thymine. DNA and RNA molecules are polymers made up of long chains of nucleotides.
Patch-Clamp Technique: An experimental method in electrophysiology that allows the study of single or multiple ion channels in cells. It is often used to investigate the functional properties of SCN2A channels.
Pharmacogenomics: The study of how genes affect a person's response to drugs. Understanding SCN2A mutations can inform pharmacogenomic approaches to treat related disorders.
Phenotype: The observable physical properties of an organism; these include the organism's appearance, development, and behavior. In the context of SCN2A, it refers to the specific symptoms and characteristics resulting from the mutation.
Phenotypic Spectrum: The range of physical manifestations and symptoms that can result from mutations in a specific gene. SCN2A mutations can lead to a wide phenotypic spectrum, including epilepsy, intellectual disability, and autism.
Precision Medicine: A medical model that proposes the customization of healthcare, with medical decisions, practices, and/or products being tailored to the individual patient. In the context of SCN2A, this could involve targeted treatments based on specific genetic mutations.
Protein Expression: The process by which proteins are synthesized, modified, and regulated in living organisms. Altered protein expression of the SCN2A gene can lead to disease.
SCN2A: A gene located on chromosome 2 that encodes the alpha subunit of the voltage-gated sodium channel Nav1.2, critical for the proper functioning of neuronal signaling. Seizure: A sudden, uncontrolled electrical disturbance in the brain, which can cause changes in behavior, movements, feelings, and levels of consciousness.
Sodium Channel: A protein in the cell membrane that allows sodium ions to enter the cell, crucial for generating and transmitting electrical signals in neurons. Stop Codon: A stop codon is a sequence of three nucleotides in DNA or messenger RNA (mRNA) that signals a halt to protein synthesis in the cell. There are 64 different trinucleotide codons: 61 specify amino acids and 3 are stop codons (i.e., UAA, UAG and UGA).
Substitution: Substitution, as related to genomics, is a type of mutation in which one nucleotide is replaced by a different nucleotide. The term can also refer to the replacement of one amino acid in a protein with a different amino acid.
Symptomatic Treatment: Therapy aimed at alleviating symptoms rather than addressing the underlying cause of a disorder. Many treatments for SCN2A-related disorders are currently symptomatic.
Synaptic Transmission: The process by which a nerve cell communicates with another cell. SCN2A mutations can disrupt normal synaptic transmission by altering sodium channel function.
Therapeutic Target: A molecule or gene that has been identified as a potential point of intervention for treatment. SCN2A is considered a therapeutic target for drug development in certain neurological disorders.
Truncating Mutation: Mutations that lead to a shortened protein product. Some SCN2A mutations are truncating, leading to a non-functional or absent sodium channel.
Variant of Uncertain Significance: When analysis of a patient’s genome identifies a variant, but it is unclear whether that variant is actually connected to a health condition, the finding is called a variant of uncertain significance (abbreviated VUS). In many cases, these variants are so rare in the population that little information is available about them. Typically, more information is required to determine if the variant is disease related.
Voltage-Gated Sodium Channel (VGSC): A type of ion channel located in the cell membrane that opens in response to changes in electrical potential, allowing sodium ions to flow into the neuron, thus initiating an action potential.
Wild Type: The phenotype with respect to a given inherited characteristic that is considered to be the "normal" type commonly found in natural populations. Used in research as a standard to measure variation.