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A novel CFHR5 fusion protein causes C3 glomerulopathy in a family without Cypriot ancestry

Title: A novel CFHR5 fusion protein causes C3 glomerulopathy in a family without Cypriot ancestry
Authors: Medjeral-Thomas, N
Malik, TH
Patel, MP
Toth, T
Cook, HT
Tomson, C
Pickering, MC
Item Type: Journal Article
Abstract: C3 glomerulopathy describes glomerular pathology associated with predominant deposition of complement C3 including dense deposit disease and C3 glomerulonephritis. Familial C3 glomerulonephritis has been associated with rearrangements affecting the complement factor H–related (CFHR) genes. These include a hybrid CFHR3-1 gene and an internal duplication within the CFHR5 gene. CFHR5 nephropathy, to date, occurred exclusively in patients with Cypriot ancestry, and is associated with a heterozygous internal duplication of the CFHR5 gene resulting in duplication of the exons encoding the first two domains of the CFHR5 protein. Affected individuals possess both the wild-type nine-domain CFHR5 protein (CFHR512-9) and an abnormally large mutant CFHR5 protein in which the initial two protein domains are duplicated (CFHR51212-9). We found CFHR51212-9 in association with familial C3 glomerulonephritis in a family without Cypriot ancestry. The genomic rearrangement was distinct from that seen in Cypriot CFHR5 nephropathy. Our findings strengthen the association between CFHR51212-9 and familial C3 glomerulonephritis and recommend screening for CFHR51212-9 in patients with C3 glomerulopathy irrespective of ethnicity. Since CFHR51212-9 can result from at least two genomic rearrangements, screening is most readily achieved through analysis of CFHR5 protein.
Issue Date: 1-Apr-2014
Date of Acceptance: 12-Jul-2013
URI: http://hdl.handle.net/10044/1/87722
DOI: 10.1038/ki.2013.348
ISSN: 0085-2538
Publisher: Elsevier
Start Page: 933
End Page: 937
Journal / Book Title: Kidney International
Volume: 85
Issue: 4
Copyright Statement: © 2013 International Society of Nephrology. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 098476/Z/12/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
COMPLEMENT FACTOR-H
MUTATION
INSIGHTS
Adult
Complement C3
Complement System Proteins
Female
Glomerulonephritis, Membranoproliferative
Humans
Male
Middle Aged
Humans
Glomerulonephritis, Membranoproliferative
Adult
Middle Aged
Complement System Proteins
Complement C3
Female
Male
Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
COMPLEMENT FACTOR-H
MUTATION
INSIGHTS
1103 Clinical Sciences
Urology & Nephrology
Publication Status: Published
Online Publication Date: 2015-12-16
Appears in Collections:Department of Immunology and Inflammation



This item is licensed under a Creative Commons License Creative Commons