Challis, Rachel C., Araujo, Geisilaine S. R., Wong, Edwin K. S., Anderson, Holly E., Awan, Atif, Dorman, Anthony M., Waldron, Mary, Wilson, Valerie, Brocklebank, Vicky, Strain, Lisa, Morgan, B. Paul ORCID: https://orcid.org/0000-0003-4075-7676, Harris, Claire L., Marchbank, Kevin J., Goodship, Timothy H. J. and Kavanagh, David 2016. A de novo deletion in the regulators of complement activation cluster producing a hybrid complement factor H/complement factor H-related 3 gene in atypical hemolytic uremic syndrome. Journal of the American Society of Nephrology 27 (6) , pp. 1617-1624. 10.1681/ASN.2015010100 |
Abstract
The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H–related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology–mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Uncontrolled Keywords: | complement; hemolytic uremic syndrome; genetic renal disease |
Publisher: | American Society of Nephrology |
ISSN: | 1046-6673 |
Date of Acceptance: | 7 September 2015 |
Last Modified: | 02 Nov 2022 11:24 |
URI: | https://orca.cardiff.ac.uk/id/eprint/101898 |
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