A frame shift mutation in the fibrinogen A alpha chain gene in a kindred with renal amyloidosis.
A new American kindred with amyloidosis was found by single-strand conformation polymorphism analysis to have a mutation in the fibrinogen A alpha chain gene. Affected members in this kindred have autosomal dominant amyloid nephropathy. DNA sequencing showed a single nucleotide deletion at the third base of codon 524 of the fibrinogen A alpha chain genes (4904delG) that resulted in a frame shift and premature termination of the protein at codon 548. Antiserum was produced to a portion of the abnormal peptide predicted by the DNA sequence and amyloid deposits were immuno-histologically proven to contain this abnormal peptide. Two of the propositus' 4 children were positive for the mutant fibrinogen A alpha chain gene by restriction fragment length polymorphism analysis based on polymerase chain reaction. These two mutant gene carriers now in the second decade of life show no clinical symptoms of amyloidosis as yet but have lower plasma fibrinogen concentrations when compared with their normal siblings. This the first description of a kindred with renal amyloidosis and low plasma fibrinogen and also the first report of amyloidosis caused by a frame shift mutation.
Uemichi
T
T
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Liepnieks
J J
JJ
Yamada
T
T
Gertz
M A
MA
Bang
N
N
Benson
M D
MD
D000328:Adult; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D000686:Amyloidosis / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology; D002648:Child; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational
D000682:Amyloid; D003062:Codon; D010446:Peptide Fragments; D005340:Fibrinogen