A French kindred with autosomal dominant hereditary renal amyloidosis was found to have a novel mutation in the fibrinogen Aα-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 Aα-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 Aα-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 amine acid substitutions that give hereditary renal amyloidosis. Ever transplantation to stop synthesis of this abnormal hepatic derived protein should be considered early in the course of the disease.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Dec 15 1997|
ASJC Scopus subject areas
- Cell Biology