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

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

Full text not available from this repository.

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
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

Citation Data

Cited 30 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item