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Importance of Genetic Testing in the Diagnosis of Transthyretin Cardiac Amyloidosis

      Systemic amyloidosis results from extracellular deposition of fibrillar material derived from aggregation of precursor proteins into insoluble beta-pleated sheets. The most frequently recognized types are due to prolonged inflammation, deposition of immunoglobulin light chains, and accumulation of transthyretin, a tetrameric protein synthesized in the liver. Transthyretin amyloidosis can occur owing to wild-type or autosomal-dominant mutant transthyretin and predominantly affects the heart and peripheral nervous system. We present here 2 cousins with rapidly progressive cardiomyopathy secondary to TTR p.Val40Ile, a rare variant with high penetrance.
      • Bauer R.
      • Dikow N.
      • Brauer A.
      • et al.
      The “Wagshurst study”: p.Val40Ile transthyretin gene variant causes late-onset cardiomyopathy.
      Before genetic testing, each was thought to have an alternative diagnosis.
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