Cardiac failure in transthyretin (TTR) amyloidosis patients has been shown
to be caused by different mutations in the TTR gene. In the present case, a
73-year-old man from Northern Sweden was evaluated for heart failure. Amyl
oid deposits were found in subcutaneous fat and in intestinal biopsies. The
presence of a variant form of TTR was detected in the plasma by electrospr
ay ionisation mass spectrometry (ESI-MS). The mutation was located by singl
e-strand conformation polymorphism (SSCP) analysis of the TTR gene where a
band shift was seen in exon 2. Direct sequencing of exon 2 revealed a singl
e base-pair substitution (G1724T). This transversion results in an amino ac
id substitution at codon 45, alanine to serine (ATTRAla45Ser). Mass spectro
metry analysis excluded that the variant is a polymorphism, since no simila
r shift in molecular weight has been present in more than 200 control sampl
es. Congo red and immunostaining of duodenum biopsy specimens confirmed the
presence of systemic ATTR amyloidosis, and clinical examination, including
echocardiography, found evidence of a restrictive cardiomyopathy. He had 1
0 years previously been operated for a bilateral carpal tunnel syndrome, bu
t otherwise no symptoms were present that could be attributed to his system
ic amyloidosis. No axonal polyneuropathy was noted at nerve conduction stud
ies. This novel mutation is the second amyloidogenic TTR mutation found in
the Swedish population.