A 4-year-old girl developed clumsiness and difficulty ambulating over 6 months. On physical examination, she showed difficulty with balance while walking, dysarthria, poor hand coordination, absent deep tendon reflexes, and a bilateral Babinski sign. Light touch and vibratory sensation were greatly diminished. There was no muscular weakness. Over the next 5 years, she developed congestive heart failure from hypertrophic cardiomyopathy. She also had hyperglycemia. At autopsy, there was increased perinuclear iron deposition within cardiac myocytes. Which of the following genetic abnormalities with trinucleotide repeat expansions was most likely present in this patient?
She had Friedreich ataxia, an autosomal recessive progressive illness that most often has an onset in the first decade of life. The frataxin gene encodes for a protein involved in iron regulation in cells, and a GAA trinucleotide repeats expansion results in decreased protein and decreased mitochondrial oxidative phosphorylation. The other options listed have no cardiac involvement. Mutations of the huntingtin gene are seen with Huntington disease marked by choreoathetosis beginning in young to middle-aged adults. Increased tandem repeats in the FMR1 gene account for cases of fragile X syndrome characterized by mental retardation. The dystrophila myotonia-protein kinase gene is abnormal in cases of myotonic dystrophy with muscular weakness and dementia.
CAG repeats in the huntingtin gene
CGG repeats in the FMR1 gene
CTG repeats in the dystrophila myotonia-protein kinase gene
GAA repeats in the frataxin gene
Central Nervous System