Cardiac amyloidosis: report of a patient heterozygous for the transthyretin isoleucine 122 variant

Abstract

Amyloid fibril material was extracted from autopsy material of a patient who died from progressive cardiac failure at age 64. He had enlarged heart on routine X-ray at age 47 and the first symptoms of cardiac failure at age 62. Fractionation of the fibril material resolved peptide fragments immunoreactive with anti-human transthyretin (TTR). One of the peptides was further purified by high-performance liquid chromatography (HPLC) and subjected to tryptic peptide mapping along with TTR isolated from the patient's serum. In both instances, sequencing procedures revealed, in addition to the normal peptide 12 (residues 105-126), an abnormal peptide with an isoleucine for valine substitution at position 122. This substitution has been described previously in a patient with systemic senile amyloidosis (SSA) homozygous for this variant. The results question whether SSA is a clinical entity related to TTR Ile 122 with phenotypic expression in the homozygous condition.