Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis

J Vis Exp. 2018 Jun 9:(136):57743. doi: 10.3791/57743.

Abstract

Genetic testing is the most reliable test for hereditary transthyretin related amyloidosis and should be performed in most cases of transthyretin amyloidosis (ATTR). ATTR is a rare but fatal disease with heterogeneous phenotypes; therefore, the diagnosis is sometimes delayed. With increasing attention and broader recognition on early manifestations of ATTR as well as emerging treatments, appropriate diagnostic studies, including the transthyretin (TTR) genetic test, to confirm the types and variants of ATTR are therefore fundamental to improve the prognosis. Genetic analyses with polymerase chain reaction (PCR) methods confirm the presence of TTR point mutations much more quickly and safer than conventional methods such as southern blot. Herein, we demonstrate genetic confirmation of the ATTR Ala97Ser mutation, the most common endemic mutation in Taiwan. The protocol comprises four main steps: collecting whole blood specimen, DNA extraction, genetic analysis of all four TTR exons with PCR, and DNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Amyloid Neuropathies, Familial / genetics*
  • Amyloid Neuropathies, Familial / pathology
  • Female
  • Genetic Testing / methods*
  • Humans
  • Male
  • Polymerase Chain Reaction / methods*
  • Sequence Analysis, DNA / methods*

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related