Demonstration of a circulating 65K gelsolin variant specific for familial amyloidosis, Finnish type.
Familial amyloidosis, Finnish type (FAF), is a dominantly inherited form of systemic amyloidosis caused by a point mutation G654 to A654 in the gelsolin gene. The mutation leads to the expression of mutant Asn-187 gelsolin and the accumulation of amyloid in tissues. Here we demonstrate that patients with FAF have an abnormal 65K gelsolin species in the circulation that cosegregates with the disease. The 65K variant is detected by immunoblotting using a monoclonal antigelsolin antibody or polyclonal antipeptide (P-gel 231-242) antibodies. The 65K gelsolin variant is lacking in normal subjects and unaffected family members. It is the putative circulating precursor of tissue amyloid in FAF.
Fourth Department of Medicine, University of Helsinki, Finland.
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Maury
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Rossi
D000483:Alleles; D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics*; D001216:Asparagine; D001483:Base Sequence; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D002846:Chromatography, Affinity; D003062:Codon / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005387:Finland; D018260:Gelsolin; D014644:Genetic Variation; D006801:Humans; D008840:Microfilament Proteins / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017354:Point Mutation; D012016:Reference Values
D000682:Amyloid; D002135:Calcium-Binding Proteins; D003062:Codon; D018260:Gelsolin; D008840:Microfilament Proteins; D001216:Asparagine