A French kindred with autosomal dominant hereditary renal amyloidosis was found 
to have a novel mutation in the fibrinogen Aalpha-chain gene. In this kindred, 
renal disease appeared early in life and led to terminal renal failure at an 
early age. Renal transplantation resulted in rapid destruction of the allograft 
by amyloid deposition within 2 years. Amyloid fibril protein isolated from a 
transplanted kidney was found to contain a novel, hybrid peptide of 49 residues 
whose N-terminal 23 amino acids were identical to residues 499 to 521 of normal 
fibrinogen Aalpha-chain. The remainder of the peptide (26 residues) represented 
a completely new sequence for mammalian proteins. DNA sequencing documented that 
the new sequence was the result of a single nucleotide deletion at position 4897 
of the fibrinogen Aalpha-chain gene that gives a frame-shift at codon 522 and 
premature termination at codon 548. The contributions toward fibrillogenesis of 
the two portions of the amyloid fibril protein, ie, N-terminal fibrinogen 
sequence and C-terminal novel sequence, are presently unknown. However, the 
early onset and rapid reoccurrence of amyloid in renal transplants is unlike the 
clinical course with other amyloid proteins having single amino acid 
substitutions that give hereditary renal amyloidosis. Liver transplantation to 
stop synthesis of this abnormal hepatic derived protein should be considered 
early in the course of the disease.