An on-line assay for clinical detection of amyloidogenic transthyretin variants directly from serum

Abstract
We report here for the first time the on-line analysis of transthyretin genetic variants by mass spectral analysis. The use of mass spectrometry to analyze immunoprecipitated transthyretin has been previously described. However, the on-line analysis of TTR directly from serum reported here will allow for a fully automated high throughput analysis. Mutations in the plasma tranport protein TTR are readily observed and distinguished from normal TTR. Free TTR as well as TTR-cysteine and TTR-cysteinylglycine adducts are clearly evident. The resulting assay from serum to final interpretation requires jess than twenty minutes. The assay should be an effective first line discriminator of patients who are being considered to have Familial Amyloidotic Polyneuropathy (FAP) and an adjunct to definitive diagnosis by sequencing of the TTR gene or protein.

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