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

  1. Lookup NU author(s)
  2. Rachel Challis
  3. Dr Edwin Wong
  4. Dr Holly Anderson
  5. Dr Valerie Wilson
  6. Dr Vicky Brocklebank
  7. Professor Claire Harris
  8. Dr Kevin Marchbank
  9. Professor Tim Goodship
  10. Professor David Kavanagh
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
JournalJournal of the American Society of Nephrology
Year2016
Volume27
Issue6
Pages1617-1624
ISSN (print)1046-6673
ISSN (electronic)1533-3450
Full text is available for this publication:
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.
PublisherAmerican Society of Nephrology
URLhttp://dx.doi.org/10.1681/ASN.2015010100
DOI10.1681/ASN.2015010100
PubMed id26490391
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