Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain.
Three members of a family who died with renal amyloidosis were found to share a single nucleotide substitution in the fibrinogen alpha-chain gene. The predicted arginine to leucine mutation (Arg554Leu) was proven by amino acid sequence analysis of amyloid fibril protein isolated from postmortem kidney of an affected individual. Direct genomic DNA sequencing and restriction fragment length polymorphism analysis demonstrated that all three affected individuals had the guanine to thymine 4993 transversion. This is the first demonstration of hereditary amyloidosis associated with a variant fibrinogen alpha-chain. Variants of circulating fibrinogen may be the cause of a number of systemic amyloidoses with primarily renal involvement.
Benson
M D
MD
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Liepnieks
J
J
Uemichi
T
T
Wheeler
G
G
Correa
R
R
D000328:Adult; D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology; D001120:Arginine; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D007930:Leucine; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D005340:Fibrinogen; D004247:DNA; D001120:Arginine; D007930:Leucine