Deletion of Complement Factor H Related Genes CFHR1 and CFHR3 is Associated with an Increased Risk of Atypical Hemolytic Uremic Syndrome

Zipfel, Peter F.; Edey, Matthew; Heinen, Stefan; Józsi, Mihály; Richter, Heiko; Misselwitz, Joachim; Höppe, Bernd; Routledge, Danny; Strain, Lisa; Hughes, Anne E.; Goodship, Judith A.; Licht, Christoph; Goodship, Tim; Skerka, Christine

doi:10.1371/journal.pgen.0030041.eor

Cited by 5 publications

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“…The 22 CFHR1/CFHR3-deficient patients of the Jena cohort include 16 CFH autoantibody-positive and 6 patients who have no autoantibodies to CFH. The frequency of the deficient group without CFH autoantibodies is 4% in this cohort and thus slightly higher than in the Jena and Newcastle control groups (2% each) 14 or in the Iowa, Columbia, and Finnish AMD study cohorts (2.7%, 3.0%, and 2.5%, respectively). 18 Concurrence of 2 risk factors in development of aHUS has been reported for combined mutations in either the CFI and the MCP genes 19 or for various CFH haplotypes.…”

Section: Frequency Of Cfh Autoantibodiesmentioning

confidence: 51%

“…14 Information regarding the patients is summarized in Document S1 (available on the Blood website; see the Supplemental Materials link at the top of the online article).…”

Section: Patientsmentioning

confidence: 99%

“…10,11 In addition, CFH gene conversion, deletion of the complement factor H-related genes CFHR1 and CFHR3 by nonallelic homologous recombination, and the presence of CFH autoantibodies have been reported in aHUS patients. [12][13][14][15][16] These diverse scenarios are responsible for approximately 50% of the reported cases, indicating that additional factors contribute to aHUS. On the surface of human cells, multiple regulators control complement activation.…”

Section: Introductionmentioning

confidence: 99%

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Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency

Józsi

Licht

Strobel

et al. 2008

Blood

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330

303

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Section: Frequency Of Cfh Autoantibodiesmentioning

confidence: 51%

“…14 Information regarding the patients is summarized in Document S1 (available on the Blood website; see the Supplemental Materials link at the top of the online article).…”

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency

Józsi

Licht

Strobel

et al. 2008

Blood

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330

303

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“…36 The latter has been shown to result in the deletion of genes encoding the fH-related proteins (CFHR1, CFHR3, and CFHR4) 8,10 and the formation of hybrid genes (CFH/CFHR1). 6 These genomic disorders could be considered as being forms of "macrohomology."…”

Section: Discussionmentioning

confidence: 99%

“…7 We have also shown that NAHR in this region leads to deletions incorporating CFHR3/CFHR1 and CFHR1/CFHR4, which are associated with the presence of fH autoantibodies in aHUS. [8][9][10] We routinely use multiplex ligation-dependent probe amplification (MLPA) 11 to screen for genomic disorders in aHUS. In this study, we report the finding of a deletion in the C terminal region of CFH in a large aHUS family.…”

Section: Introductionmentioning

confidence: 99%

A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome

Francis

McNicholas

Awan

et al. 2012

Blood

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Genomic disorders affecting the genes encoding factor H (fH) and the 5 factor H related proteins have been described in association with atypical hemolytic uremic syndrome. These include deletions of CFHR3, CFHR1, and CFHR4 in association with fH autoantibodies and the formation of a hybrid CFH/CFHR1 gene. These occur through nonallelic homologous recombination secondary to the presence of large segmental duplications (macrohomology) in this region. Using multiplex ligation-dependent probe amplification to screen for such genomic disorders, we have identified a large atypical hemolytic uremic syndrome family where a deletion has occurred through microhomologymediated end joining rather than nonallelic homologous recombination. In the 3 affected persons of this family, we have shown that the deletion results in formation of a CFH/CFHR3 gene. We have shown that the protein product of this is a 24 SCR protein that is secreted with normal fluid-phase activity but marked loss of complement regulation at cell surfaces despite increased heparin binding. In this study, we have therefore shown that microhomology in this area of chromosome 1 predisposes to disease associated genomic disorders and that the complement regulatory function of fH at the cell surface is critically dependent on the structural integrity of the whole molecule. (Blood. 2012;119(2):591-601)

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Factor H-autoantibodies in atypical hemolytic uremic syndrome

Strobel¹,

Dahse²,

Liu³

et al. 2007

Molecular Immunology

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Deletion of Complement Factor H Related Genes CFHR1 and CFHR3 is Associated with an Increased Risk of Atypical Hemolytic Uremic Syndrome

Cited by 5 publications

References 0 publications

Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency

Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency

A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome

Factor H-autoantibodies in atypical hemolytic uremic syndrome

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