Characterization of the kidney amyloid subunit protein in a case of hereditary renal amyloidosis associated with a Glu526Val fibrinogen Aα-chain mutation

We have previously described four kindreds with hereditary renal amyloidosis having a common adenine to thymine mutation at position 4909 of the fibrinogen A alpha-chain gene, and identified the resulting Glu526Val A alpha-chain variant in plasma fibrinogen. However, insufficient tissue was available for amyloid characterization. We now report the characterization of the amyloid subunit protein isolated from the kidney of an affected individual. The amino acid sequence was determined by analysis of tryptic peptides from the subunit protein. To date, residues 509 to 580 of fibrinogen A alpha-chain have been identified with only the variant Val at residue 526. The amyloid protein also contained some hydroxy-Pro at positions 511 and 546. The results support the hypothesis that only the variant A alpha-chain is deposited in amyloid.