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
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- Rachel C. Challis
- Institutes of Genetic Medicine and
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- Geisilaine S.R. Araujo
- Institutes of Genetic Medicine and
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- Edwin K.S. Wong
- Institutes of Genetic Medicine and
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- Holly E. Anderson
- Institutes of Genetic Medicine and
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- Atif Awan
- Department of Nephrology, Our Lady’s Children’s Hospital, Crumlin, Dublin;
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- Anthony M. Dorman
- Department of Renal Pathology, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland; and
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- Mary Waldron
- Department of Nephrology, Our Lady’s Children’s Hospital, Crumlin, Dublin;
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- Valerie Wilson
- Institutes of Genetic Medicine and
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- Vicky Brocklebank
- Institutes of Genetic Medicine and
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- Lisa Strain
- Institutes of Genetic Medicine and
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- B. Paul Morgan
- Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
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- Claire L. Harris
- Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
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- Kevin J. Marchbank
- Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;
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- Timothy H.J. Goodship
- Institutes of Genetic Medicine and
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- David Kavanagh
- Institutes of Genetic Medicine and
説明
<jats:p>The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (<jats:italic toggle="yes">CFH</jats:italic>) and five complement factor H–related (<jats:italic toggle="yes">CFHR</jats:italic>) 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 <jats:italic toggle="yes">CFH/CFHR3</jats:italic> hybrid gene secondary to a <jats:italic toggle="yes">de novo</jats:italic> 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 <jats:italic toggle="yes">de novo</jats:italic> event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.</jats:p>
収録刊行物
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- Journal of the American Society of Nephrology
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Journal of the American Society of Nephrology 27 (6), 1617-1624, 2015-10-21
Ovid Technologies (Wolters Kluwer Health)
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詳細情報 詳細情報について
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- CRID
- 1361137044202108416
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- ISSN
- 15333450
- 10466673
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- データソース種別
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- Crossref