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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.


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.

SUBMITTER: Challis RC 

PROVIDER: S-EPMC4884102 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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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.

Challis Rachel C RC   Araujo Geisilaine S R GS   Wong Edwin K S EK   Anderson Holly E HE   Awan Atif A   Dorman Anthony M AM   Waldron Mary M   Wilson Valerie V   Brocklebank Vicky V   Strain Lisa L   Morgan B Paul BP   Harris Claire L CL   Marchbank Kevin J KJ   Goodship Timothy H J TH   Kavanagh David D  

Journal of the American Society of Nephrology : JASN 20151021 6


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 ge  ...[more]

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