title: Renal amyloidosis associated with a novel sequence variant of gelsolin.
abstract: We present a case of a 75-year-old woman who presented with progressive kidney failure. Kidney biopsy performed to determine the cause of kidney failure showed amyloidosis of undetermined type. Laser microdissection of the Congo Red-positive glomeruli followed by mass spectrometry studies showed a large number of spectra matching apolipoprotein E, serum amyloid P component, and gelsolin, consistent with a diagnosis of gelsolin-associated renal amyloidosis. Sequencing of the gelsolin gene revealed a previously undescribed sequence variant, a guanine to adenine substitution at nucleotide 580 of the coding sequence, corresponding to a predicted glycine to arginine mutation at amino acid 194. Gelsolin amyloidosis typically involves the nerves and skin, with only rare reported involvement of the kidney. An atypical finding on electron microscopy was that of a swirling pattern of the amyloid fibrils. The novel gelsolin variant may be responsible for the unusual clinical and pathologic presentation. The report also highlights the usefulness of laser microdissection and mass spectrometry in the typing of difficult cases of amyloidosis.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. sethi.sanjeev@mayo.edu
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.forename: Patrick
authors.initials: P
authors.lastname: Quint
authors.forename: William
authors.initials: W
authors.lastname: Maierhofer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Edward W
authors.initials: EW
authors.lastname: Highsmith
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D005260:Female; D018260:Gelsolin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D051437:Renal Insufficiency / Q000209:etiology
chemical_list: D018260:Gelsolin