What is the inheritance pattern and genetic basis of Friedreich ataxia?

What is the inheritance pattern and genetic basis of Friedreich ataxia?

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

Answer: (C)

Friedreich ataxia is inherited in an autosomal recessive pattern and is caused by a GAA trinucleotide repeat expansion in the FXN gene. This expansion reduces the production of frataxin, a mitochondrial protein, leading to neurodegeneration and the typical clinical features. Since two mutated copies are necessary for disease, carriers are usually asymptomatic. Most cases involve expansions on both alleles, though a disease allele can pair with a different mutation on the other allele and still be autosomal recessive. The other options are incorrect because a dominant pattern would require only one mutated copy to cause disease, and the specific repeats mentioned (CAG, CGG) are associated with other disorders (Huntington disease and Fragile X, respectively).

Friedreich ataxia is inherited in an autosomal recessive pattern and is caused by a GAA trinucleotide repeat expansion in the FXN gene. This expansion reduces the production of frataxin, a mitochondrial protein, leading to neurodegeneration and the typical clinical features. Since two mutated copies are necessary for disease, carriers are usually asymptomatic. Most cases involve expansions on both alleles, though a disease allele can pair with a different mutation on the other allele and still be autosomal recessive. The other options are incorrect because a dominant pattern would require only one mutated copy to cause disease, and the specific repeats mentioned (CAG, CGG) are associated with other disorders (Huntington disease and Fragile X, respectively).