A specific test for transthyretin 122 (Val----Ile), based on PCR-primer-introduced restriction analysis (PCR-PIRA): confirmation of the gene frequency in blacks.
The variant transthyretin (TTR) allele, TTR (122 Val----Ile), associated with cardiac amyloidosis in blacks, is caused by a G----A transition which destroys a MaeIII site. This variant has previously been detected by PCR around codon 122, followed by MaeIII digestion, but this test is not specific: any of 12 mutations in the MaeIII recognition site, each of which yields a different amino acid change, would also destroy this site. A modification of PCR, termed "PCR-primer-introduced restriction analysis," was used to introduce a new FokI site into the PCR products derived from the variant (122 Ile) but not wild-type (122 Val) allele. This test demonstrated that each of six previously identified MaeIII(-) alleles had lost its MaeIII site because of a G----A transition encoding TTR (122 Val----Ile), confirming that the same TTR variant was present both in 4/177 healthy black individuals and as a homozygous variant in an individual with cardiac amyloidosis.
Jacobson
D R
DR
Research Service, New York Veterans Administration Medical Center, NY 10010.
D000483:Alleles; D000686:Amyloidosis / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D009202:Cardiomyopathies / Q000235:genetics; D004247:DNA / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000235:genetics*; D015183:Restriction Mapping; D014633:Valine / Q000235:genetics
D011228:Prealbumin; D007532:Isoleucine; D004247:DNA; C040838:endodeoxyribonuclease MaeIII; D015252:Deoxyribonucleases, Type II Site-Specific; D014633:Valine