Manifestation of atypical hemolytic uremic syndrome caused by novel mutations in MCP
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Dana Provaznikova & Simon Rittich & Michal Malina & Tomas Seeman & Iuri Marinov & Magdalena Riedl & Ingrid Hrachovinova
- چاپ و سال / کشور: 2011
Description
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 Mutations, as yet unpublished, were widely distributed over the gene (SCR2 domain, signal peptide, and cytoplasmic region).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.
Pediatr Nephrol DOI 10.1007/s00467-011-1943-5 Received: 16 November 2010 / Revised: 11 May 2011 / Accepted: 17 May 2011
