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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

Lookup NU author(s): Rachel Challis, Dr Edwin Wong, Dr Holly Anderson, Dr Valerie Wilson, Dr Vicky Brocklebank, Professor Claire Harris, Professor Kevin MarchbankORCiD, Professor Tim Goodship, Professor David KavanaghORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Society of Nephrology, 2016.

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The Regulators of Complement Activation cluster at chromosome 1q32 contains the genes encoding the complement regulator factor H and five factor H related proteins. This is an area of the genome that 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 haemolytic uraemic syndrome, arising commonly through non-allelic homologous recombination (NAHR). We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3kb deletion which arose through microhomology mediated end joining rather than NAHR. We confirm a transcript from this hybrid gene and demonstrate a secreted protein product. Lacking the recognition domain of factor H, this hybrid protein has impaired cell surface complement regulation. That this arose as a de novo event suggests that this is a dynamic area of the genome where further genomic disorders may arise.

Publication metadata

Author(s): Challis RC, Araujo GSR, Wong EKS, Anderson HE, Awan A, Dorman AM, Waldron M, Wilson V, Brocklebank V, Strain L, Morgan BP, Harris CL, Marchbank KJ, Goodship THJ, Kavanagh D

Publication type: Article

Publication status: Published

Journal: Journal of the American Society of Nephrology

Year: 2016

Volume: 27

Issue: 6

Pages: 1617-1624

Print publication date: 01/06/2016

Online publication date: 21/10/2015

Acceptance date: 07/09/2015

Date deposited: 10/03/2016

ISSN (print): 1046-6673

ISSN (electronic): 1533-3450

Publisher: American Society of Nephrology


DOI: 10.1681/ASN.2015010100

PubMed id: 26490391


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Funder referenceFunder name
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
305608European Union
G0701325United Kingdom Medical Research Council