Fredrich’s ataxia is caused by which type of mutation
## **Core Concept**
Friedreich's ataxia is a genetic disorder caused by mutations in the *FXN* gene, which encodes frataxin, a protein crucial for mitochondrial function. This disorder primarily affects the nervous system and is characterized by progressive damage to the spinal cord, peripheral nerves, and the cerebellum. The mutation leads to impaired production of frataxin, resulting in mitochondrial dysfunction and increased oxidative stress.
## **Why the Correct Answer is Right**
The correct answer involves an **expansion of a GAA trinucleotide repeat** within the first intron of the *FXN* gene. This expansion leads to epigenetic changes and transcriptional silencing of the *FXN* gene, resulting in reduced or absent production of frataxin. The lack of frataxin disrupts mitochondrial function, particularly in cells with high energy demands like neurons and muscle cells, leading to the clinical manifestations of Friedreich's ataxia.
## **Why Each Wrong Option is Incorrect**
- **Option A:** Point mutations typically involve a change in a single nucleotide and can lead to various genetic disorders. However, Friedreich's ataxia is specifically associated with a trinucleotide repeat expansion, not a point mutation.
- **Option B:** While chromosomal translocations can cause genetic disorders by disrupting gene function, Friedreich's ataxia is not caused by a translocation but by a specific type of repeat expansion.
- **Option C:** Deletions involve the loss of genetic material and can cause a wide range of disorders. However, the primary cause of Friedreich's ataxia is not a deletion but an expansion of a GAA repeat.
## **Clinical Pearl / High-Yield Fact**
A key clinical pearl for Friedreich's ataxia is that it often presents in childhood or adolescence with progressive ataxia, dysarthria, and loss of reflexes. A notable feature is the presence of **hypertrophic cardiomyopathy** in many patients, which is a major cause of morbidity and mortality. Early diagnosis and management are crucial, and the disease is one of the most common causes of autosomal recessive ataxia.
## **Correct Answer:** . Expansion of a GAA trinucleotide repeat