Two New DNA-Based Tests for Mutations Causing Familial Amyloidotic Polyneuropathy

Thyroxine-binding prealbumin (TBPA) has been isolated from amyloid fibrils from several kindreds with familial amyloidotic polyneuropathy (FAP), and subjected to amino acid sequencing. Mutations have been described at several positions in different families. Amyloid material from an Israeli patient with FAP (“SKO”) has been studied in two laboratories, which reported two different mutations: a position 49 substitution of glycine for threonine(l) and a a position 33 substitution of isoleucine for phenylalanine(2). The position 33 mutation, corresponding to a T to A substitution at the first position of the codon, would lead to a predicted restriction fragment length polymorphism (RFLP) using the restriction enzyme Bcl I (figure 1). We examined DNA isolated from autopsy material from SKO to attempt to clarify the mutation present. We have also studied DNA from an unrelated kindred with FAP (“SMA”) which had not been previously studied biochemically.