Direct sequencing of the gene for Maryland/German familial amyloidotic polyneuropathy type II and genotyping by allele-specific enzymatic amplification.

Direct genomic DNA sequencing has been used to characterize the mutation associated with familial amyloidotic polyneuropathy in the Maryland/German kindred. A mutation of thymine to adenine in the prealbumin (transthyretin) gene at the position corresponding to the second base of codon 58 in the prealbumin mRNA gives a histidine for leucine substitution in the plasma protein. Since the mutation does not result in a change in the restriction pattern of the prealbumin gene, a new method for the direct detection of single base changes in genomic DNA was developed using the polymerase chain reaction and an allele-specific oligonucleotide primer.