Analysis Of MCP Mutations In 9 Chinese Children With Hemolytic Uremic Syndrome

ObjectiveThe hemolytic uremic syndrome(HUS) is characterized by the triad of thrombocytopenia,microangiopathic hemolytic anaemia and acute renal failure.HUS may be classified as diarrhoeal-associated HUS(D+HUS)or non-diarrhoeal/atypical HUS(aHUS).It occurs in children aged from 6 months to 3 years old and is also a common cause of rapid progression to end-stage renal failure.Recent advances have shown that aHUS is a disease of complement dysregulation. Presently,approximately 50%of patients with aHUS have been demonstated to have mutations in the genes of complent components and reguators(CFH,CFB,CFI,MCP and C3),highly suggesting that impaired control of the activity of the complement amplification convertase C3bBb is the predominant factor predisposing individuals to the disease.MCP is a widely espressed transmembrance glycolprotein that regulates complement activation by serving as a membrance-bound cofactor for the plasma serine protease CFI to cleave C3b.More than twenty muations in MCP have been described in the cases with aHUS.Mutations in MCP account for up to 13%of aHUS patients.In addition,genetic variability in MCP is associated with aHUS.To investigate a possible relationship between MCP mutation and the hemolytic uremic syndrome(HUS),genetic mutation analysis was done on HUS with patients.MethodsNine Southern Chinese children with HUS were included in the study with the informed consents.Genomic DNA samples were extracted from peripheral blood cells of these HUS patients.All the 14 exons,exon-intron boundaries of MCP were detected in the patients by polymerse chain reaction(PCR) and direct sequencing. Fifty genomic DNA 50 healthy volunteers were selected as a normal control group. RusuitsNo mutations in MCP in all 14 exons and exon-intron boundaries were identified in the 9 southern Chinese children with HUS.However,a polymorphism (IVS9-78G＞A) was detected in some of the patients and the controls.There was significant difference in the allelic frequencies of IVS9-78G＞A between the patients and 50 controls.ConclusionWe analyzed all 14 exons,exon-intron boundaries of MCP of 9 patients with HUS and found no causative mutations in MCP in them,which suggests that MCP mutations are not a major cause of 9 patients with aHUS.But the polymorphism of the MCP gene,IVSg-78G＞A,may be a predisposing factor for HUS in the study.