Which mutation type is characteristic of Friedreich ataxia?

Which mutation type is characteristic of Friedreich ataxia?

• A. Autosomal recessive; GAA trinucleotide repeat expansion in FXN gene.
• B. Autosomal dominant; CGG repeat expansion in FXN gene.
• C. X-linked; CGG repeat expansion in FXN gene.
• D. Mitochondrial; A3243G mutation in FXN gene.

Answer: (A)

Friedreich ataxia is driven by a GAA trinucleotide repeat expansion in the FXN gene, and this condition is inherited in an autosomal recessive pattern. The long GAA repeats reduce expression of the frataxin protein, a mitochondrial protein essential for iron-sulfur cluster biogenesis. With less frataxin, neurons in the dorsal columns and spinocerebellar pathways, as well as cardiac muscle, become vulnerable, leading to the characteristic ataxia, sensory loss, and often hypertrophic cardiomyopathy. This mode of mutation—an unstable trinucleotide repeat expansion causing gene silencing—is why the autosomal recessive, GAA expansion answer is the best fit. The other options describe different genes or inheritance patterns (for example, CGG repeats in the FMR1 gene on the X chromosome for Fragile X, or a mitochondrial A3243G mutation associated with MELAS), which do not describe Friedreich ataxia.

Friedreich ataxia is driven by a GAA trinucleotide repeat expansion in the FXN gene, and this condition is inherited in an autosomal recessive pattern. The long GAA repeats reduce expression of the frataxin protein, a mitochondrial protein essential for iron-sulfur cluster biogenesis. With less frataxin, neurons in the dorsal columns and spinocerebellar pathways, as well as cardiac muscle, become vulnerable, leading to the characteristic ataxia, sensory loss, and often hypertrophic cardiomyopathy.

This mode of mutation—an unstable trinucleotide repeat expansion causing gene silencing—is why the autosomal recessive, GAA expansion answer is the best fit. The other options describe different genes or inheritance patterns (for example, CGG repeats in the FMR1 gene on the X chromosome for Fragile X, or a mitochondrial A3243G mutation associated with MELAS), which do not describe Friedreich ataxia.