Huntington disease is caused by a trinucleotide repeat expansion in the coding region of the HTT gene on chromosome 4. Specifically, a CAG repeat in exon 1 of the HTT gene leads to the production of a mutant huntingtin protein with an expanded polyglutamine tract. This results in:
Gain-of-function toxicity: The mutant protein disrupts cellular processes, leading to neuronal dysfunction and death.
Progressive neurodegeneration: Primarily affecting the basal ganglia and cortex, causing motor, cognitive, and psychiatric symptoms.
Since the mutation occurs in the coding region of the gene, it directly alters the protein product, making Huntington disease a classic example of a disorder caused by DNA changes in the coding region.
Incorrect Answers
Fragile X syndrome
– Fragile X syndrome is caused by a CGG trinucleotide repeat expansion in the 5′ untranslated region (UTR) of the FMR1 gene. This expansion leads to hypermethylation and silencing of the gene, resulting in a loss of the FMRP protein.
– Why it’s wrong: The mutation is in the non-coding region (UTR), not the coding region.
Epilepsy
– Epilepsy is a heterogeneous disorder with multiple causes, including genetic, structural, metabolic, and immune factors. While some forms of epilepsy are linked to mutations in coding regions of genes (e.g., ion channel genes), epilepsy as a whole is not specifically caused by DNA changes in the coding region.
– **Why it’s wrong**: Epilepsy is not exclusively linked to coding region mutations.
Friedreich ataxia
– Friedreich ataxia is caused by a **GAA trinucleotide repeat expansion** in the **intron** of the **FXN gene**. This expansion leads to reduced expression of the frataxin protein, which is involved in mitochondrial iron homeostasis.
– Why it’s wrong: The mutation is in the non-coding region (intron), not the coding region.
Myotonic dystrophy- Myotonic dystrophy type 1 is caused by a CTG trinucleotide repeat expansion in the 3′ untranslated region (UTR) of the DMPK gene. This expansion leads to RNA toxicity and misregulation of RNA-binding proteins.
– Why it’s wrong: The mutation is in the non-coding region (UTR), not the coding region.