Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene: ATTR Ala45Ser

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.