title: Manifestation of atypical hemolytic uremic syndrome caused by novel mutations in MCP.
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 Mutations, as yet unpublished, were widely distributed over the gene (SCR2 domain, signal peptide, and cytoplasmic region).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.
authors.affiliation: Coagulation laboratory, Institute of Hematology and Blood Transfusion, 128 20 Prague 2, Czech Republic. D.provaz@centrum.cz
authors.forename: Dana
authors.initials: D
authors.lastname: Provaznikova
authors.forename: Simon
authors.initials: S
authors.lastname: Rittich
authors.forename: Michal
authors.initials: M
authors.lastname: Malina
authors.forename: Tomas
authors.initials: T
authors.lastname: Seeman
authors.forename: Iuri
authors.initials: I
authors.lastname: Marinov
authors.forename: Magdalena
authors.initials: M
authors.lastname: Riedl
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hrachovinova
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D065766:Atypical Hemolytic Uremic Syndrome; D002648:Child; D018153:Czech Republic; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006098:Granulocytes / Q000276:immunology; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011379:Prognosis; D012008:Recurrence; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C497857:CD46 protein, human; D051916:Membrane Cofactor Protein