A novel CFHR5 fusion protein causes C3 glomerulopathy in a family without Cypriot ancestry.
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| 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 (CFHR5(12-9)) and an abnormally large mutant CFHR5 protein in which the initial two protein domains are duplicated (CFHR5(1212-9)). We found CFHR5(1212-9) 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 CFHR5(1212-9) and familial C3 glomerulonephritis and recommend screening for CFHR5(1212-9) in patients with C3 glomerulopathy irrespective of ethnicity. Since CFHR5(1212-9) can result from at least two genomic rearrangements, screening is most readily achieved through analysis of CFHR5 protein.
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| Authors | Nicholas Medjeral-Thomas, Talat H Malik, Mitali P Patel, Tibor Toth, H Terence Cook, Charles Tomson, Matthew C Pickering |
| Journal | Kidney international (Kidney Int) Vol. 85 Issue 4 Pg. 933-7 (Apr 2014) ISSN: 1523-1755 [Electronic] United States |
| PMID | 24067434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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