A DOUBLE-VARIANT TRANSTHYRETIN ALLELE (SER-6, ILE-33) IN THE ISRAELI PATIENT SKO WITH FAMILIAL AMYLOIDOTIC POLYNEUROPATHY

Transthyretin (TTR) isolated from amyloid fibrils from an Israeli pati ent (''SKO'') with familial amyloidotic polyneuropathy has been studie d by two groups of investigators. Originally, a position 49 Thr-->Gly substitution was reported; subsequently, a position 33 Phe-->Ile subst itution was found instead. We have studied DNA from this patient by si ngle strand conformation polymorphism analysis, restriction analysis, and DNA sequencing. On one allele, exon 2 contained both a T-->A trans version at the first position of codon 33, encoding the previously des cribed Phe-->Ile substitution, and a G-->A transition at the first pos ition of codon 6, encoding a Gly-->Ser substitution. The originally re ported position 49 mutation was not encoded in the genomic DNA. This i s the first report of a TTR double variant allele in a patient with TT R amyloidosis. (C) 1994 Wiley-Liss, Inc.