Rowczenio, D;
Stensland, M;
de Souza, GA;
Strøm, EH;
Gilbertson, JA;
Taylor, G;
Rendell, N;
... Wien, TN; + view all
(2017)
Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein.
Kidney International Reports
, 2
(3)
pp. 461-469.
10.1016/j.ekir.2016.11.005.
Preview |
Text
1-s2.0-S246802491630170X-main.pdf - Published Version Download (1MB) | Preview |
Abstract
INTRODUCTION: Fibrinogen A alpha chain amyloidosis is an autosomal dominant disease associated with mutations in the fibrinogen A alpha chain (FGA) gene, and it is the most common cause of hereditary renal amyloidosis in the UK. Patients typically present with kidney impairment and progress to end-stage renal disease over a median time of 4.6 years. METHODS: Six patients presented with proteinuria, hypertension, and/or lower limb edema and underwent detailed clinical and laboratory investigations. RESULTS: A novel FGA gene mutation was identified in each case: 2 frameshift mutations F521Sfs*27 and G519Efs*30 and 4 single base substitutions G555F, E526K, E524K, R554H. In 5 subjects, extensive amyloid deposits were found solely within the glomeruli, which stained specifically with antibodies to fibrinogen A alpha chain, and in one of these cases, we found coexistent fibrinogen A alpha chain amyloidosis and anti-glomerular basement membrane antibody disease. One patient was diagnosed with light-chain amyloidosis after a bone marrow examination revealed a small clonal plasma cell population, and laser microdissection of the amyloid deposits followed by liquid chromatography and tandem mass spectrometry identified kappa light chain as the fibril protein. DISCUSSION: We report 6 novel mutations in the FGA gene: 5 were associated with renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to light-chain amyloid deposits discovered in a patient with a plasma cell dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis corroborated by genetic analysis and adequate typing using combined immunohistochemistry and laser microdissection and mass spectrometry is valuable to avoid misdiagnosis, especially when a family history of amyloidosis is absent.
| Type: | Article |
|---|---|
| Title: | Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ekir.2016.11.005 |
| Publisher version: | https://doi.org/10.1016/j.ekir.2016.11.005 |
| Language: | English |
| Additional information: | Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | anti-GBM glomerulonephritis; end-stage renal disease (ESRD); fibrinogen A alpha chain; hereditary renal amyloidosis; mass spectrometry-based proteomics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1568168 |
Archive Staff Only
 |
View Item |
