Second Department of Internal Medicine, Osaka University Medical School, Japan.
A to G transversion was identified in exon 4 of transthyretin gene in familial amyloidotic polyneuropathy in two sibling cases living in Osaka. This transversion led to the replacement of tyrosine by cysteine residue at codon 114 of 127 residue molecule. This identification was achieved by randomly sequencing recombinant clones containing the entire length of each one of the four exons selectively amplified by polymerase chain reaction. Dot blot analysis with allele-specific oligonucleotides indicated the linkage of this mutation with the disease and confirmed the single base change.