Hereditary renal amyloidosis with a novel variant fibrinogen.
Two families with hereditary renal amyloidosis were found to have a novel mutation in the fibrinogen A alpha chain gene. This form of amyloidosis is an autosomal dominant condition characterized by proteinuria, hypertension, and subsequent azotemia. DNAs of patients with amyloidosis were screened for a polymorphism in fibrinogen A alpha chain gene by single-strand conformation polymorphism analysis, and affected individuals from two kindreds were found to have a mutation. Both of these kindreds are American of Irish descent presenting with non-neuropathic, nephropathic amyloidosis in the fifth to the seventh decade of life. DNA sequencing showed a point mutation in the fibrinogen A alpha chain gene that is responsible for substitution of valine for glutamic acid at position 526. By restriction fragment length polymorphism analysis, 7 affected individuals and 14 asymptomatic individuals in these two kindreds were positive for the fibrinogen A alpha chain Val 526 gene. Fibrinogen was isolated from plasma of a heterozygous gene carrier and shown to contain approximately 50% variant fibrinogen. Discovery of this new mutation confirms the association between fibrinogen A alpha chain variant and hereditary renal amyloidosis and establishes a new biochemical subtype of amyloidosis.
Uemichi
T
T
Department of Medicine, Indiana University, Indianapolis.
Liepnieks
J J
JJ
Benson
M D
MD
D000368:Aged; D000682:Amyloid / Q000032:analysis; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic
D000682:Amyloid; D017931:DNA Primers; D005340:Fibrinogen