A new test for detection ot the his 58 variant transthyretin allele in hereditary amyloidosis; creation of diagnostic restriction endonuclease recognition sites by PCR based mutagenesis

Steven R. Zeldenrust, Merrill D. Bensonf

Research output: Contribution to journalArticle

8 Scopus citations


A new test has been developed to detect the His 58 variant transthyretin allele associated with familial amyloidotic polyneuropathy type II in the Maryland/German kindreds. Since the point mutation identified in this disease does not alter the restriction pattern of the TTR gene, previous DNA testing had been accomplished through the use ofallele-specific amplification. In order to increase the accuracy of the testing process and allow detection of individuals homozygous for the mutation, an alternative technique utilizing polymerase chain reaction-mediated site-directed mutagenesis has been developed to produce a unique restriction site in the PCR product derived from the His 58 variant allele. This method, which we have termed PCR-In-duced Mutation Restriction Analysis (PCR-IMRA), maybe applied to the detection of nearly all single base changes in genomic DNA which fail to produce a restriction fragment length polymorphism. A strategy for devising diagnostic tests by this method is presented.

Original languageEnglish (US)
Pages (from-to)154-159
Number of pages6
Issue number3
StatePublished - Jan 1 1994



  • Amyloidosis
  • Polymerase chain reaction (Pcr)-Mutagenesis
  • Transthyretin

ASJC Scopus subject areas

  • Internal Medicine

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