Molecular basis for factor H and FHL-1 deficiency in an Italian family

Sánchez-Corral, Pilar; Bellavia, Daniele; Amico, Luisa; Brai, M.; Córdoba, Santiago Rodrı́guez de

doi:10.1007/s002510050631

Cited by 24 publications

(10 citation statements)

References 26 publications

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“…In another study, three Italian factor H-deficient patients were homozygous for a nonsense mutation (G638T), which changes a GAA codon for residue Glu171 to a TAA termination codon (Glu171) which is located within SCR3 of factor H. This mutation resulted in the complete absence of factor H and factor H-like protein 1 in the patients' plasma [109].…”

Section: Human Deficiency Of Factor Hmentioning

confidence: 99%

Clinical Aspects and Molecular Basis of Primary Deficiencies of Complement Component C3 and its Regulatory Proteins Factor I and Factor H

2006

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The complement system participates in both innate and acquired immune responses. Deficiencies in any of the protein components of this system are generally uncommon and require specialized services for diagnosis. Consequently, complement deficiencies are clinically underscored and may be more common than is normally estimated. As C3 is the major complement component and participates in all three pathways of activation, it is fundamental to understand all the clinical consequences observed in patients for which this protein is below normal concentration or absent in the serum. C3 deficiencies are generally associated with higher susceptibility to severe infections and in some cases with autoimmune diseases such as systemic lupus erythematosus. Here, we review the main clinical aspects and the molecular basis of primary C3 deficiency as well as the mutations in the regulatory proteins factor I and factor H that result in secondary C3 deficiencies. We also discuss the use of animal models to study these deficiencies.

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Section: Human Deficiency Of Factor Hmentioning

confidence: 99%

Clinical Aspects and Molecular Basis of Primary Deficiencies of Complement Component C3 and its Regulatory Proteins Factor I and Factor H

2006

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“…The monoclonal antibody 35H9 recognizes fH and CFHL1 and has been described previously. 27 Working dilutions of the antibodies were 1:10 000 (MoAb 35H9), 1:50 000 (␣CFHR1), 1:30 000 (␣CFHR3/4), and 1:100000 (␣CFHR5).…”

Section: Description Of Primary Antibodiesmentioning

confidence: 99%

Characterization of complement factor H–related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome

Abarrategui-Garrido

Martı́nez-Barricarte

López-Trascasa

et al. 2009

Blood

189

230

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The factor H-related protein family (CFHR) is a group of minor plasma proteins genetically and structurally related to complement factor H (fH). Notably, deficiency of CFHR1/CFHR3 associates with protection against age-related macular degeneration and with the presence of anti-fH autoantibodies in atypical hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to analyze the CFHR proteins in plasma samples from controls, patients with aHUS, and patients with type II membranoproliferative glomerulonephritis. Here, we report on the identification of persons carrying novel deficiencies of CFHR1, CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies, suggesting that generation of these antibodies is specifically related to CFHR1 deficiency. We also report the characterization of a novel CFHR1 polymorphism, resulting from a gene conversion event between CFH and CFHR1, which strongly associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity to fH, may compete with fH, decreasing protection of cellular surfaces against complement damage. In summary, our comprehensive analyses of the CFHR proteins have improved our understanding of these proteins and provided further insights into aHUS pathogenesis. (Blood. 2009;114:4261-4271)

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“…Some cases of systemic lupus erythematosus have also been reported in patients exhibiting combined FH and C2 deficiency (14,15). Some FH-deficient patients presented with increased susceptibility to meningococcal infection, probably secondary to acquired C3 or terminal components C5 to C9 deficiencies (16 -18).…”

mentioning

confidence: 99%

“…Additional genetic studies have also found several different heterozygous missense mutations between SCR 16 and 20, suggesting a particular role of the C-terminal domains of the protein in the pathophysiology of HUS (20 -24). However, the molecular mechanism of FH deficiencies has only been demonstrated in five patients (15,19,21,22,25) and involved SCR 1, 2, 3, 9, 16, and 20 .…”

mentioning

confidence: 99%

Heterozygous and Homozygous Factor H Deficiencies Associated with Hemolytic Uremic Syndrome or Membranoproliferative Glomerulonephritis

Dragon-Durey¹,

Frémeaux‐Bacchi

Loirat

et al. 2004

Journal of the American Society of Nephrology

343

259

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Molecular basis for factor H and FHL-1 deficiency in an Italian family

Cited by 24 publications

References 26 publications

Clinical Aspects and Molecular Basis of Primary Deficiencies of Complement Component C3 and its Regulatory Proteins Factor I and Factor H

Clinical Aspects and Molecular Basis of Primary Deficiencies of Complement Component C3 and its Regulatory Proteins Factor I and Factor H

Characterization of complement factor H–related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome

Heterozygous and Homozygous Factor H Deficiencies Associated with Hemolytic Uremic Syndrome or Membranoproliferative Glomerulonephritis

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