A new transthyretin variant (Ser23Asn) associated with familial amyloidosis in a Portuguese patient

The detection and characterization of a new transthyretin (ATTR) variant Se r23Asn, associated with cardiomyopathy in a Portuguese patient with familia l amyloidosis is described. Isoelectricfocusing (IEF) of serum from the pro positus demonstrated heterozygosity for the presence of wild type and varia nt ATTR. A combination of mass spectrometric (MS) analyses, including elect rospray ionization mass spectrometry (ESI MS), high performance liquid chro matography (HPLC)/ESI MS and matrix-assisted laser desorption/ionization ma ss spectrometry (MALDI MS) performed on the serum-derived TTR were used to identify and locate the amino acid replacement in the variant protein. Gene tic mutation analysis by DNA sequencing and allele-specific PCR confirmed t his finding.