A new amyloidogenic transthyretin variant, [D38A], detected by electrospray ionization mass spectrometry

A new variant of transthyretin (TTR) was detected by mass spectrometry (MS) in a 63-year-old Japanese female patient suffering from amyloidosis. TTR w as analyzed by 2-dimensional liquid chromatography coupled with electrospra y ionization MS. Variant TTR showed extra peaks in addition to normal TTR p eaks. The extra peaks were about 44 Da smaller than normal TTR peaks, and t he abundance of variant peaks showed about 80% of the corresponding normal free and adduct peaks. Direct genomic DNA sequencing of TTR exon 2 showed b oth adenine and cytosine in the position corresponding to the second base o f codon 38. This codes for a variant alanine (GCT) as well as the normal as partic acid (GAT), indicating that the case is heterozygous for the substit ution, [D38A].