Introduction:
Ataxia is a term used for a group of disorders that affect balance and coordination. The Ataxin 2 ATXN2 gene is one of the few genes independently responsible for causing several diseases. Ataxin 2 gene displays the property of polymorphism (presents itself in various forms), making it a powerful modulator of neurological diseases. The same gene can cause a variety of disorders.
What Are Genes?
A gene is the basic structural and functional unit of heredity. Genes are made up of DNA (deoxyribonucleic acid). DNA is present in the nucleus of the cell. The DNA molecules are tightly packed or coiled in a thread-like pattern known as the chromosome. The structure of chromosomes is histone proteins packed with DNA strands. Histone proteins provide structural support to the chromosomes. Each chromosome has a pair of X and Y chromosomes known as the sex chromosomes. Sex chromosomes are responsible for determining the sex of an individual.
What Is Ataxin 2 Gene?
Ataxin 2 (ATXN2) gene produces a protein called ataxin-2. The ataxin 2 protein is present in the cytoplasm (liquid present inside the cells) of the cells. This protein is found throughout the body. Ataxin-2 protein plays the role of translating genetic information to produce proteins. Researchers also state that the ataxin-2 protein is involved in processing RNA (ribonucleic acid). RNA is similar to DNA (deoxyribonucleic acid). The function of RNA is to convert the information stored in DNA into proteins. Mutations (changes in structure) in the ataxin 2 gene cause systemic disorders. When there are mutations in the ataxin 2 gene, there is abnormal production of the protein ataxin 2. Abnormality in the protein ataxin 2 causes neurological disorders.
How Does Ataxin 2 Gene Play a Role in the Development of Neurological Disorders?
The Ataxin 2 gene consists of a DNA segment called the CAG trinucleotide repeat. This CAG trinucleotide consists of three DNA building blocks: cytosine, adenine, and guanine. In normal cases, the CAG segment is repeated 22 times in a gene. In the mutated ataxin 2 gene, the CAG segment is repeated more than 30 times. This increases the length of the CAG segment and causes the development of neurological disorders. Abnormality in the length of the CAG segment leads to abnormal function of the ataxin 2 protein.
The altered function of the ataxin 2 protein causes cell death. An increase in the length of the CAG segment causes the following neurological disorders -
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Spinocerebellar ataxia Type 2.
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Parkinson's disease.
What Is the Pathophysiology of Spinocerebellar Ataxia Type 2?
This condition is caused by CAG trinucleotide repeat expansion in the DNA segment of the Ataxin 2 gene. This is a progressive disease characterized by problems with the motor functions of the body. Individuals with this disease show loss of brain cells as the abnormal protein Ataxin 2 causes cell death. The brain cells known as Purkinje cells (a large, branched type of nerve cell found in the cortex of the cerebellum) are sensitive to the abnormal Ataxin 2 protein. The Purkinje cells are present in the cerebellum. The Purkinje cells become less with advancement in age. The cerebellum controls all motor movements, such as balance and coordination, speech, memory, and learning. The abnormal Ataxin 2 protein will cause the death of the Purkinje cells and affect the function of the cerebellum.
The following are symptoms of spinocerebellar ataxia type 2 -
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Problem with balance and coordination leading to unsteady gait (walking).
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Slurred speech
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Involuntary movements of the eyes.
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Poor hand-eye coordination
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Difficulty in learning new things and remembering them.
This condition has no specific cure. Relieving the symptoms is the only way to manage this disease.
What Is Amyotrophic Lateral Sclerosis?
This condition is caused by degeneration and death of the neurons that are involved in motor function. The motor neurons transmit impulses from the brain and spinal cord to the muscles to perform functions. When these motor neurons degenerate, an abnormal transmission of impulses to the muscles leads to impaired motor function. Mutations in the Ataxin 2 gene can cause this condition. The protein Ataxin 2 is associated with abnormal protein Ataxin 2, which causes cell death in the brain tissue, subsequently causing the degeneration of neurons.
The symptoms of this disease include -
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Muscle weakness or stiffness is seen initially. Gradually, all the voluntary muscles are affected, and there is difficulty in carrying out functions like breathing, eating, and swallowing.
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Muscle twitching in the shoulders, arms, legs, or tongue (small muscle contractions in the body).
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Difficulty in chewing and swallowing.
Physicians may prescribe medications to treat the symptoms of this disease. Physical therapy is beneficial to restore muscle strength and function.
What Is the Role of Ataxin 2 Gene in Parkinson's Disease?
Parkinson's disease is an age-related degenerative neurological condition. Parkinson's disease is characterized by nerve cell damage in the brain. This damage to nerves causes dopamine levels to drop. Dopamine is a chemical neurotransmitter that sends impulses from the brain to the organs associated with motor function. Abnormal Ataxin 2 protein leads to cell death in the brain tissue, which is associated with Parkinson's disease.
How Is the Abnormal Ataxin 2 Gene Identified in an Individual?
Molecular genetic testing is a reliable method to identify this gene and its types in an individual.
Molecular genetic testing, also known as molecular diagnostics or molecular testing, is a type of medical testing that focuses on studying and analyzing the structure, function, and alterations of genes at the molecular level. It involves the analysis of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), and proteins to identify genetic variations, mutations, or other abnormalities that may be associated with specific diseases or conditions. This test can be used to determine the causative agent in symptomatic patients.
Conclusion:
Ataxin gene 2 plays a critical role in the inheritance of neurodegenerative disorders. These disorders have no specific cure. The treatment consists of managing the symptoms to provide symptomatic relief. These disorders are progressive, and the symptoms get worse with age. However, medications are available to treat the symptoms that make the prognosis of these conditions better. Supportive therapy and nutritional support will prove to be beneficial for patients. Recent advances in molecular genetic testing will make diagnosing these conditions easier.
