Related Experiment Video
Updated: May 20, 2026
10:31
Antigenic Liposomes for Generation of Disease-specific Antibodies
Published on: October 25, 2018
A candidate gene for autoimmune myasthenia gravis
Guida Landouré1, Melanie A Knight, Horia Stanescu
1Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Neurology
|June 30, 2012
Summary
A genetic mutation in the ecto-NADH oxidase 1 (ENOX1) gene is linked to familial autoimmune myasthenia gravis. This variant reduces ENOX1 expression, potentially causing the autoimmune condition in affected individuals.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- Autoimmune myasthenia gravis (MG) can have a familial component.
- Parental consanguinity in affected families suggests a genetic basis for MG.
- Identifying causative mutations is crucial for understanding disease mechanisms.
Purpose of the Study:
- To identify the causative genetic mutation in a family with multiple siblings affected by adult-onset autoimmune myasthenia gravis.
- To investigate the role of a specific gene variant in the pathogenesis of familial MG.
Main Methods:
- Genome-wide homozygosity mapping was performed to identify shared genetic regions among affected siblings.
- Candidate gene sequencing and functional studies, including quantitative and allele-specific reverse transcriptase PCR (RT-PCR), were conducted.
- The expression levels of the ecto-NADH oxidase 1 (ENOX1) gene and its variant transcript were analyzed in affected individuals and controls.
Main Results:
- A homozygous single nucleotide variant was identified in the 3'-untranslated region of the ENOX1 gene in affected siblings.
- This ENOX1 variant was absent in 764 healthy controls.
- Quantitative RT-PCR revealed significantly reduced ENOX1 expression (approx. 20% of normal) in homozygous individuals and reduced mRNA stability in heterozygotes.
Conclusions:
- The identified sequence variant in the ENOX1 gene is strongly associated with familial autoimmune myasthenia gravis.
- Reduced ENOX1 expression due to this variant may contribute to the development of autoimmune myasthenia in affected patients.
- This finding provides a potential genetic marker and therapeutic target for familial MG.
Related Concept Videos
01:22Myasthenia Gravis ll: Pathophysiology
The disease process of myasthenia gravis begins at the neuromuscular junction, where antibodies attack key proteins needed for muscle activation. This immune reaction weakens signal transmission, leading to the characteristic muscle fatigue and weakness that define the condition.Immune-Mediated DamageIn most individuals, antibodies target acetylcholine receptors (AChRs) on the postsynaptic membrane of muscle cells. By blocking acetylcholine binding, these antibodies prevent the nerve signal...
01:20Myasthenia Gravis: Overview and Treatment
Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness and increased fatigability of skeletal muscles. It is an autoimmune disease affecting approximately one in 2000 people, where antibodies against the α1 subunit of nicotinic acetylcholine receptors are produced.
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which leads...
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which leads...
01:15Myasthenia Gravis: Diagnostic Tests
Myasthenia gravis is an autoimmune condition affecting neuromuscular transmission, causing generalized weakness in skeletal muscles. Initial diagnoses rely on patients' signs, symptoms, and medical history. The challenge lies in distinguishing myasthenia from other muscular dystrophies. An important diagnostic feature is the significant improvement of symptoms after administering anticholinesterase inhibitors.
The edrophonium test is a diagnostic tool for myasthenia gravis. It involves...
The edrophonium test is a diagnostic tool for myasthenia gravis. It involves...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:10Muscle Contraction
In skeletal muscles, acetylcholine is released by nerve terminals at the motor endplate—the point of synaptic communication between motor neurons and muscle fibers. The binding of acetylcholine to its receptors on the sarcolemma allows entry of sodium ions into the cell and triggers an action potential in the muscle cell. Thus, electrical signals from the brain are transmitted to the muscle. Subsequently, the enzyme acetylcholinesterase breaks down acetylcholine to prevent excessive muscle...