Transthyretin mass determination for detection of transthyretin familial amyloid.

  • O'Brien J
  • Bergen H
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The concentration range of plasma proteins exceeds the dynamic range of any single analytical method. It has been estimated that the concentration range of serum proteins exceeds ten orders of magnitude (1). Because of this, prior immunoselection of even abundant proteins facilitates the relative nonquantitative observations required to show structural abnormality in primary or in posttranslational structure. Determination of atypical proteins by mass measurement has been reported for genetic defects in glycosylation (2, 3) and for monitoring for transthyretin (TTR) defects (4). Here we describe a rapid method of purification and electrospray introduction of TTR into a mass spectrometer to detect mass changes due to amino acid substitutions. The method currently forms the basis for a clinical assay to ascertain TTR mutations resulting in amyloidosis.

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  • John F. O'Brien

  • H. Robert Bergen

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