title: Three German fibrinogen Aalpha-chain amyloidosis patients with the p.Glu526Val mutation.
abstract: Plasma protein fibrinogen variants cause fibrinogen A alpha-chain (AFib) amyloidosis, which presents with hypertension, proteinuria, and azotemia. Six AFib mutations have been reported thus far. We identified three patients who presented with marked proteinuria and serum creatinine elevations. Their kidney biopsies revealed destruction of the glomerular architecture by amyloid deposits with typical, apple-green birefringence in polarized light after Congo red staining. We found immunoreactivity against fibrinogen, which is typical for this type of amyloidosis. We sequenced the FGA exon 5 and demonstrated heterozygosity for the p.Glu526Val mutation in all three cases. This amino acid substitution is the most common fibrinogen A alpha-chain variant causing AFib amyloidosis. The mutation has been reported in individuals of European and American descent but not yet in German patients. AFib amyloidosis should therefore be considered an important differential diagnosis in German patients with renal amyloidosis. In the cases described here, the use of antibodies directed against fibrinogen, followed by direct gene sequencing, revealed the underlying cause.
authors.affiliation: Department of Pathology, Charité University Hospital, Charitéplatz 1, Berlin, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Eriksson
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
authors.forename: Raoul
authors.initials: R
authors.lastname: Bergner
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000686:Amyloidosis / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D001706:Biopsy; D003937:Diagnosis, Differential; D005091:Exons / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005858:Germany; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D044465:White People / Q000208:ethnology / Q000235:genetics
chemical_list: C464794:fibrinogen Aalpha; D005340:Fibrinogen