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Georg Dewald - One of the best experts on this subject based on the ideXlab platform.
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Complement factor 7 gene mutations in relation to meningococcal infection and clinical recurrence of meningococcal disease.
Molecular immunology, 2009Co-Authors: Taco W. Kuijpers, Georg Dewald, Melanie Nguyen, C. T. P. Hopman, Ed Nieuwenhuys, Arjan C. Lankester, Anja Roos, Arie Van Der Ende, Cees Fijen, Martin De BoerAbstract:Abstract Meningococcal disease is caused by Neisseria meningitidis which is associated with high morbidity and mortality. Recurrences of meningococcal infection have been observed in patients with terminal Complement Component defects, because of the inefficient formation of the lytic membrane attack complex (MAC), C5b-9. Complement Component C7 is one of the five plasma proteins to form the MAC. The gene C7 may carry mutations that cause functional abnormalities or the mere absence of the C7 protein. More than 200 patients were screened for aberrant C7 protein by isoelectric focusing (C7 IEF). These were compared with patients in whom recurrent meningococcal infection had resulted in the diagnosis of complete C7 absence (C7Q0). A higher proportion of C7 IEF variants were found in meningitis cases compared to controls ( p = 0.03). In contrast to C7Q0 patients, recurrent meningococcal infection was never observed in C7 IEF cases. Whereas C7Q0 sera were defective in meningococcal serogroup B and W135 killing assays, the sera of patients with C7 IEF variants were only defective in Complement-mediated killing when classical pathway activation by (endogenous) anti-meningococcal antibodies was blocked. Upon sequence analysis we characterized the genetic background of the C7*6 and C7*8 IEF pattern and identified three novel C7 gene mutations in 13 C7Q0 patients. In conclusion, C7 IEF variants can determine meningococcal killing in the early stage of infection when antibody-independent killing prevails. The results endorse the lack of clinical recurrences once antibodies are present, whereas in C7Q0 patients the anti-meningococcal antibodies may not suffice to protect from recurrent meningococcal infection.
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a common ser thr polymorphism in the perforin homologous region of human Complement Component C7
Human Heredity, 1994Co-Authors: Georg Dewald, Markus M. Nöthen, Katja RütherAbstract:Complement Component C7 plays an important role in the formation of the membrane attack complex of the Complement system. Here we describe a novel polymorphism of human C7, namely a nucleotide sequence polymorphism changing codon 367 from AGT (encoding Ser) to ACT (encoding Thr). Using the polymerase chain reaction, the polymorphism is easily detectable either as a MaeIII restriction fragment length polymorphism or by single-strand conformation analysis. The two alleles are both very common, probably in all major races.
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A Common Ser/Thr Polymorphism in the Perforin-Homologous Region of Human Complement Component C7
Human heredity, 1994Co-Authors: Georg Dewald, Markus M. Nöthen, Katja RütherAbstract:Complement Component C7 plays an important role in the formation of the membrane attack complex of the Complement system. Here we describe a novel polymorphism of human C7, namely a nucleotide sequence polymorphism changing codon 367 from AGT (encoding Ser) to ACT (encoding Thr). Using the polymerase chain reaction, the polymorphism is easily detectable either as a MaeIII restriction fragment length polymorphism or by single-strand conformation analysis. The two alleles are both very common, probably in all major races.
B. Sanchez - One of the best experts on this subject based on the ideXlab platform.
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Complement Component C7 deficiency in two Spanish families
Immunology, 2004Co-Authors: Sonia Barroso, A. Alvarez, Margarita López-trascasa, I. Wichmann, B. Sanchez, Amparo Lanuza, Rafael Luque, Antonio Núñez-roldánAbstract:Different genetic mutations have been described in Complement Component C7 deficiency, a molecular defect clinically associated with an increased susceptibility to neisserial recurrent infections. In this work we report the genetic basis of C7 deficiency in two different Spanish families (family 1 and family 2). In family 1, of Gypsy ethnical background, exon-specific polymerase chain reaction and sequencing revealed a not previously described single base deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father, leading to a stop codon that causes the premature truncation of the C7 protein (K416 X 419). Additionally, the patient and her mother displayed a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in a change of amino acid (G357R). This mutation was firstly described in individuals of Moroccan Sephardic Jewish ancestry and has been also reported among Spaniards. In family 2, another novel mutation was found in homozygosity in two siblings; a two base-pair deletion of nucleotides 1922 and 1923 in exon 14 leading to the generation of a downstream stop codon causing the truncation of the C7 protein product (S620 X 630). Our results provide more evidence for the heterogeneous molecular basis of C7 deficiency as well as for the subsequent susceptibility to meningococcal disease, since different families carry different molecular defects. On the other hand, certain C7 defects appear to be prevalent in individuals from certain populations or living in defined geographical areas.
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Complement Component C7 deficiency in a Spanish family
Clinical and experimental immunology, 2003Co-Authors: M F Vázquez-bermúdez, Sonia Barroso, K Walter, A. Alvarez, A Alarcón, Margarita López-trascasa, I. Wichmann, Francisco Aguilar, Antonio Núñez-roldán, B. SanchezAbstract:Different genetic mutations have been described in Complement Component C7 deficiency, a molecular defect which is clinically associated with an increased susceptibility to neisserial recurrent infections, although some cases remain asymptomatic. In this work we report the genetic bases of C7 deficiency in one Spanish family. Exon-specific PCR and sequencing revealed a novel point mutation at nucleotide 615 (exon 6) leading to a stop codon (UGG to UGA) in the patient, his mother, and sister. This transversion causes the premature truncation of the C7 protein (W183X). Additionally, we detected a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in an amino acid change (G357R) in the patient, his father, as well as in his sister. This latter mutation had been previously described in individuals from Moroccan Sephardic Jewish ancestry. Since both heterozygous mutations were found in the patient as well as in his asymptomatic sister, we analyse other meningococcal defence mechanisms such as polymorphisms of the opsonin receptors on polymorphonuclear cells. Results showed that the patient and his sister bore identical combinations of FcgammaRIIA-H/R131 and FcgammaRIIIB-NA1/2 allotypes. Our results provide further evidence that the molecular pathogenesis of C7 deficiency as well as susceptibility to meningococcal disease are heterogeneous, since different families carry different molecular defects, although many of the C7 defects appear to be homogeneous in individuals from certain geographical areas. The missense mutation G357R would make an interesting topic of analysis with regard to meningococcal disease susceptibility in the Spanish population.
Antonio Núñez-roldán - One of the best experts on this subject based on the ideXlab platform.
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Complement Component C7 deficiency in two Spanish families
Immunology, 2004Co-Authors: Sonia Barroso, A. Alvarez, Margarita López-trascasa, I. Wichmann, B. Sanchez, Amparo Lanuza, Rafael Luque, Antonio Núñez-roldánAbstract:Different genetic mutations have been described in Complement Component C7 deficiency, a molecular defect clinically associated with an increased susceptibility to neisserial recurrent infections. In this work we report the genetic basis of C7 deficiency in two different Spanish families (family 1 and family 2). In family 1, of Gypsy ethnical background, exon-specific polymerase chain reaction and sequencing revealed a not previously described single base deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father, leading to a stop codon that causes the premature truncation of the C7 protein (K416 X 419). Additionally, the patient and her mother displayed a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in a change of amino acid (G357R). This mutation was firstly described in individuals of Moroccan Sephardic Jewish ancestry and has been also reported among Spaniards. In family 2, another novel mutation was found in homozygosity in two siblings; a two base-pair deletion of nucleotides 1922 and 1923 in exon 14 leading to the generation of a downstream stop codon causing the truncation of the C7 protein product (S620 X 630). Our results provide more evidence for the heterogeneous molecular basis of C7 deficiency as well as for the subsequent susceptibility to meningococcal disease, since different families carry different molecular defects. On the other hand, certain C7 defects appear to be prevalent in individuals from certain populations or living in defined geographical areas.
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Complement Component C7 deficiency in a Spanish family
Clinical and experimental immunology, 2003Co-Authors: M F Vázquez-bermúdez, Sonia Barroso, K Walter, A. Alvarez, A Alarcón, Margarita López-trascasa, I. Wichmann, Francisco Aguilar, Antonio Núñez-roldán, B. SanchezAbstract:Different genetic mutations have been described in Complement Component C7 deficiency, a molecular defect which is clinically associated with an increased susceptibility to neisserial recurrent infections, although some cases remain asymptomatic. In this work we report the genetic bases of C7 deficiency in one Spanish family. Exon-specific PCR and sequencing revealed a novel point mutation at nucleotide 615 (exon 6) leading to a stop codon (UGG to UGA) in the patient, his mother, and sister. This transversion causes the premature truncation of the C7 protein (W183X). Additionally, we detected a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in an amino acid change (G357R) in the patient, his father, as well as in his sister. This latter mutation had been previously described in individuals from Moroccan Sephardic Jewish ancestry. Since both heterozygous mutations were found in the patient as well as in his asymptomatic sister, we analyse other meningococcal defence mechanisms such as polymorphisms of the opsonin receptors on polymorphonuclear cells. Results showed that the patient and his sister bore identical combinations of FcgammaRIIA-H/R131 and FcgammaRIIIB-NA1/2 allotypes. Our results provide further evidence that the molecular pathogenesis of C7 deficiency as well as susceptibility to meningococcal disease are heterogeneous, since different families carry different molecular defects, although many of the C7 defects appear to be homogeneous in individuals from certain geographical areas. The missense mutation G357R would make an interesting topic of analysis with regard to meningococcal disease susceptibility in the Spanish population.
Junbin Zhang - One of the best experts on this subject based on the ideXlab platform.
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A 425 T>C polymorphism in Complement C7 association with resistance to Aeromonas hydrophila in grass carp.
Genetics and molecular research : GMR, 2016Co-Authors: Yubang Shen, Junbin Zhang, R. Q. Wang, Y. F. XuanAbstract:Aeromonas hydrophila, a widespread bacterium in the aquatic environment, causes hemorrhagic septicemia in fish. In the last decade, the disease has caused mass mortalities and tremendous economic loss in cultured fish. The Complement Component C7 is a terminal Component of Complement that interacts in a sequence of polymerization reactions with other terminal Complement Components to form a membrane attack complex. The formation of the membrane attack complex creates a pore in the membranes of certain pathogen that can lead to their death. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the C7 gene and to assess their association with A. hydrophila resistance in grass carp. A resource population consisting of 186 susceptible and 191 resistant grass carp was constructed. We sequenced a total of 7826 bp of the C7 gene and identified 6 SNPs that were genotyped in the resource population. The SNP -1575 A>C was positioned in the promoter region of the gene. The SNP 425 C>T identified in the coding exon was a synonymous substitution in the fourth exon. Statistical analysis showed that SNP 425 C>T was associated with the incidence of hemorrhagic septicemia. The SNPs -1575 A>C, -688 T>C, and -266 A>C were highly linked together (r(2) > 0.85). No haplotypes generated with these 3 SNPs were associated with resistance to A. hydrophila in grass carp. These findings suggest that the 425 C>T polymorphism in C7 gene may be a significant molecular marker for resistance to A. hydrophila in grass carp.
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Expression of Complement Component C7 and involvement in innate immune responses to bacteria in grass carp.
Fish & shellfish immunology, 2012Co-Authors: Yubang Shen, Junbin ZhangAbstract:Activation of the Complement system, which forms a major part of the innate immune system, results in the formation of the terminal Complement complex. The Complement Component, C7, plays an integral role in the assembly of this complex within target cell membranes. In this study, C7 was isolated and characterized from grass carp, an important cultured fish in China. The predicted amino acid sequence of C7 cDNA (2644 bp) exhibited 55.4 and 48.3% homology with trout C7-1 and zebrafish C7, respectively. The grass carp C7 gene was consisted of 18 exons and 17 introns. C7 gene expression was detected in the trunk kidney, liver, head kidney, skin, spleen, heart and intestine. Significant changes in C7 transcript expression (>20-fold) were detected following Aeromonas hydrophila infection, indicating C7 involvement in innate immune responses to bacteria in teleost fish.
Sonia Barroso - One of the best experts on this subject based on the ideXlab platform.
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Complement Component C7 deficiency in two Spanish families
Immunology, 2004Co-Authors: Sonia Barroso, A. Alvarez, Margarita López-trascasa, I. Wichmann, B. Sanchez, Amparo Lanuza, Rafael Luque, Antonio Núñez-roldánAbstract:Different genetic mutations have been described in Complement Component C7 deficiency, a molecular defect clinically associated with an increased susceptibility to neisserial recurrent infections. In this work we report the genetic basis of C7 deficiency in two different Spanish families (family 1 and family 2). In family 1, of Gypsy ethnical background, exon-specific polymerase chain reaction and sequencing revealed a not previously described single base deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father, leading to a stop codon that causes the premature truncation of the C7 protein (K416 X 419). Additionally, the patient and her mother displayed a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in a change of amino acid (G357R). This mutation was firstly described in individuals of Moroccan Sephardic Jewish ancestry and has been also reported among Spaniards. In family 2, another novel mutation was found in homozygosity in two siblings; a two base-pair deletion of nucleotides 1922 and 1923 in exon 14 leading to the generation of a downstream stop codon causing the truncation of the C7 protein product (S620 X 630). Our results provide more evidence for the heterogeneous molecular basis of C7 deficiency as well as for the subsequent susceptibility to meningococcal disease, since different families carry different molecular defects. On the other hand, certain C7 defects appear to be prevalent in individuals from certain populations or living in defined geographical areas.
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Complement Component C7 deficiency in a Spanish family
Clinical and experimental immunology, 2003Co-Authors: M F Vázquez-bermúdez, Sonia Barroso, K Walter, A. Alvarez, A Alarcón, Margarita López-trascasa, I. Wichmann, Francisco Aguilar, Antonio Núñez-roldán, B. SanchezAbstract:Different genetic mutations have been described in Complement Component C7 deficiency, a molecular defect which is clinically associated with an increased susceptibility to neisserial recurrent infections, although some cases remain asymptomatic. In this work we report the genetic bases of C7 deficiency in one Spanish family. Exon-specific PCR and sequencing revealed a novel point mutation at nucleotide 615 (exon 6) leading to a stop codon (UGG to UGA) in the patient, his mother, and sister. This transversion causes the premature truncation of the C7 protein (W183X). Additionally, we detected a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in an amino acid change (G357R) in the patient, his father, as well as in his sister. This latter mutation had been previously described in individuals from Moroccan Sephardic Jewish ancestry. Since both heterozygous mutations were found in the patient as well as in his asymptomatic sister, we analyse other meningococcal defence mechanisms such as polymorphisms of the opsonin receptors on polymorphonuclear cells. Results showed that the patient and his sister bore identical combinations of FcgammaRIIA-H/R131 and FcgammaRIIIB-NA1/2 allotypes. Our results provide further evidence that the molecular pathogenesis of C7 deficiency as well as susceptibility to meningococcal disease are heterogeneous, since different families carry different molecular defects, although many of the C7 defects appear to be homogeneous in individuals from certain geographical areas. The missense mutation G357R would make an interesting topic of analysis with regard to meningococcal disease susceptibility in the Spanish population.