Atypical haemolytic uraemic syndrome and mutations in complement regulator genes

@article{DragonDurey2005AtypicalHU,
  title={Atypical haemolytic uraemic syndrome and mutations in complement regulator genes},
  author={Marie-Agn{\`e}s Dragon-Durey and V{\'e}ronique Fr{\'e}meaux-Bacchi},
  journal={Springer Seminars in Immunopathology},
  year={2005},
  volume={27},
  pages={359-374}
}
Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) disorder characterised by the association of haemolytic anaemia, thrombocytopenia and acute renal failure. Atypical forms (non-related to shigatoxin) may be familial or sporadic, with frequent recurrences and most of them lead to end stage renal failure. During the last years, different groups have demonstrated genetic predisposition of atypical HUS involving complement components factor H (FH), CD46 [or membrane co-factor… 
A missense mutation in factor I (IF) predisposes to atypical haemolytic uraemic syndrome
TLDR
The gloomy outcome of renal transplants in patients with an IF deficiency is confirmed, and new therapies should be evaluated in these patients.
Unraveling the complex genetics of atypical hemolytic uremic syndrome
TLDR
Screening the largest American cohort of aHUS patients for mutations in CFH, MCP, CFB, CFI, C3, THBD as well as CFHR5 identified over thirty novel mutations and suggests a more comprehensive genetic screening method that would better serve patients.
Factor I mutation in Tunisian patient with atypical hemolytic uremic syndrome
TLDR
The importance of screening patients with atypical hemolytic uremic syndrome for mutations in the CFI, CFH and MCP genes before renal transplantation is reemphasized and the challenges in the management of these patients are shown.
Atypical Hemolytic Uremic Syndrome: Update on the Complement System and What Is New
TLDR
It is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis.
Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.
TLDR
Outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group, and new therapies are urgently needed.
Atypical haemolytic-uraemic syndrome: reflecting over the old and new
TLDR
Knowledge of mutations and polymorphisms in the genes encoding the complement regulatory proteins revealed clinical importance in the management of the patients, altering not only the transplantation perspective but also leading to the search for new drugs, something that will potentially change the poor prognosis of these patients.
Inherited deficiency of membrane cofactor protein expression and varying manifestations of recurrent atypical hemolytic uremic syndrome in a sibling pair.
TLDR
It is described for the first time a disease-free individual with complete CD46 deficiency, confirming the extremely variable penetrance and genetic complexity of aHUS.
Unusual clinical severity of complement membrane cofactor protein-associated hemolytic-uremic syndrome and uniparental isodisomy.
TLDR
The outcome of the disease reported here indicates that MCP mutation and complete paternal uniparental disomy of chromosome 1 could have an additive effect in determining the severity of the HUS phenotype.
Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome.
Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS).
Case Report : Atypical Haemolytic Uraemic Syndrome Due to Abnormal Alternative Complement Pathway Regulation
Background: Atypical HUS (aHUS) occurs due to endothelial damage following abnormal complement regulation, with some cases being deficient in complement regulating factors H, I and Membrane Cofactor
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TLDR
It is proposed that reduced expression of MCP in response to complement-activating stimuli could prevent restriction of complement deposition on glomerular endothelial cells, leading to microvascular cell damage and tissue injury.
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TLDR
Two complement alternative pathway proteins, factor H (FH) and recently membrane cofactor protein (CD46; MCP) have been identified as fostering the development of atypical HUS.
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Background: The aetiology of atypical haemolytic uraemic syndrome (aHUS) is, in contrast to classical, Shiga-like toxin induced HUS in children, largely unknown. Deficiency of human complement factor
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TLDR
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TLDR
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TLDR
Factor H deficiency appears to be associated with HUS and is transmitted as an autosomal recessive trait and Persistent C3 hypocomplementemia in the setting of familial and/or recurrent HUS should be a clue to a possible inherited complement deficiency.
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TLDR
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TLDR
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TLDR
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TLDR
It is postulate that abnormalities of factor H may be involved in the etiology of HUS.
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