Identification of a new transthyretin variant (IIe49) in familial amyloidotic polyneuropathy using electrospray ionization mass spectrometry and nonisotopic RNase cleavage assay

Mutation of the transthyretin (TTR) plasma protein and gene in a Japanese p atient with amyloid polyneuropathy was investigated by electrospray ionizat ion mass spectrometry (ESI-MS) and nonisotopic RNase cleavage assay (NIRCA) , respectively. ESI-MS analysis showed normal TTR peaks and additionally a variant TTR with 12-dalton-higher molecular weight than normal TTR, NIRCA s uggested that the mutation existed near either the 5' or 3' end of exon 3, Direct DNA sequencing revealed both a normal ACC (threonine) and a variant ATC (isoleucine) at codon 49, which was located near the 5' end of exon 3. The molecular weight shift of this mutation was 12 D, consistent with the r esult of ESI-MS.