Familial C3 glomerulonephritis caused by a novel CFHR5-CFHR2 fusion gene.

Mol Immunol

Molecular Otolaryngology and Renal Research Laboratories, Caver College of Medicine, University of Iowa, Iowa City, IA, USA; Interdepartmental PhD Program in Genetics, Caver College of Medicine, University of Iowa, Iowa City, IA, USA; Departments of Pediatrics and Internal Medicine, Divisions of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Iowa Institute of Human Genetics, Caver College of Medicine, University of Iowa, Iowa City, IA, USA. Electronic address:

Published: September 2016

C3 glomerulopathy (C3G) is an ultra-rare complement-mediated renal disease characterized histologically by the predominance of C3 deposition within in the glomerulus. Familial cases of C3G are extremely uncommon and offer unique insight into the genetic drivers of complement dysregulation. In this report, we describe a patient who presented with C3G. Because a relative carried the same diagnosis, we sought an underlying genetic commonality to explain the phenotype. As part of a comprehension genetic screen, we completed multiplex ligation-dependent probe amplification across the complement factor H related region and identified amplification alterations consistent with a genomic rearrangement. Using comparative genomic hybridization, we narrowed and then cloned the rearrangement breakpoints thereby defining a novel fusion gene that is translated into a serum protein comprised of factor H related-5 (short consensus repeats 1 and 2) and factor H-related-2 (short consensus repeats 1-4). These data highlight the role of factor H related proteins in the control of complement activity and illustrate how perturbation of that control leads to C3G.

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http://dx.doi.org/10.1016/j.molimm.2016.07.007DOI Listing

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