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Manifestation of atypical hemolytic uremic syndrome caused by novel mutations in MCP

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Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations in genes encoding regulators of the alternative complement pathway (CFH, MCP, C3, CFI, CFB, THBD, and CFHR1-5) are connected with this disease. Polymorphisms (SNPs) in these genes might also influence the manifestation of aHUS. We have analyzed the genes of CFH, CFI, MCP, and C3 in a cohort of 10 unrelated Czech patients with clinically diagnosed familial aHUS. Surprisingly, 4 patients had mutations only in MCP, without mutations in any of the other genes that cause aHUS. Mutations, as yet unpublished, were widely distributed over the gene (SCR2 domain, signal peptide, and cytoplasmic region). The phenotype of the patients and their close relatives (14 individuals) was also investigated. Functional examination of MCP was also provided and proved lower expression on granulocytes in all mutations. Severity of disease varied, but onset was never earlier than 5 years of age. Penetrance of disease was 50% among carriers. We found that the severity and recurrence of the disease within families varied and might also be dependent on SNPs. Mutations in the MCP gene seems to be a common etiology of aHUS in Czech patients.

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Acknowledgements

We thank the following clinicians for their help in collecting samples: Eva Jancova, Vladimir Senigl, Sona Stepankova. This work was supported by grants from the IGA of Ministry of Health CR (NR/9258-3, NT11457-5).

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Authors and Affiliations

  1. Coagulation laboratory, Institute of Hematology and Blood Transfusion, 128 20, Prague 2, Czech Republic

    Dana Provaznikova, Simon Rittich & Ingrid Hrachovinova

  2. Department of Pediatrics, University Hospital Motol and Charles University, Prague, Czech Republic

    Michal Malina & Tomas Seeman

  3. Flow Cytometry Laboratory, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    Iuri Marinov

  4. Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria

    Magdalena Riedl

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  1. Dana Provaznikova
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  2. Simon Rittich
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  3. Michal Malina
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  4. Tomas Seeman
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  5. Iuri Marinov
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  6. Magdalena Riedl
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  7. Ingrid Hrachovinova
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Correspondence to Dana Provaznikova.

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Provaznikova, D., Rittich, S., Malina, M. et al. Manifestation of atypical hemolytic uremic syndrome caused by novel mutations in MCP . Pediatr Nephrol 27, 73–81 (2012). https://doi.org/10.1007/s00467-011-1943-5

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  • DOI: https://doi.org/10.1007/s00467-011-1943-5

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