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Pathogenic Characterization of a Novel G47R Transthyretin Mutation in Early-Onset Amyloid Cardiomyopathy - PubMed

3 hours ago
  • #G47R Mutation
  • #Transthyretin Amyloid Cardiomyopathy
  • #Tafamidis Therapy
  • A novel G47R transthyretin (TTR) mutation is linked to early-onset amyloid cardiomyopathy, causing significant structural destabilization and amyloid formation similar to aggressive variants like L55P.
  • Biophysical assays showed that both homozygous and heterozygous G47R-TTR have reduced thermodynamic and kinetic stability, and the kinetic stabilizer tafamidis effectively suppressed amyloid aggregation in vitro.
  • Plasma TTR tetramer levels were significantly lowered in symptomatic patients and asymptomatic carriers, with tafamidis treatment restoring tetramer concentrations, improving symptoms, and highlighting its potential as a biomarker for disease monitoring and therapy.