Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes

Fernie, B A; Hobart, M. J.

doi:10.1007/s004390050859

Cited by 21 publications

(26 citation statements)

References 22 publications

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“…Since these mutations lead to absence of C7 protein in the plasma, this C-terminal region is also likely to be crucial for C7 protein synthesis, secretion and/or stability [25].…”

Section: Discussionmentioning

confidence: 99%

“…Exon-specific PCR was carried out with Taq DNA polymerase (Roche Molecular Biochemicals) for the 18 exons of C7 together with their flanking introns using specific primers as previously described in [25], or newly designed: 5 0 -CTATAACTTCCAAACAGTCCC and 5 0 -CAGTTCAGCCAAAGTGAATTC for exon 0, 5 0 -CCTGAT--CCTGATGATATTTGGGGGAAT for exon 3, 5 0 -GAGCCAAT-GAGCCAATGAATAATCTTGCC for exon 4, 5 0 -TTGCTTTG-TGCTTTGTGCCAATGAAGAG for exon 6, 5 0 -CCACAGTAGCTA-CCACAGTAGCTATAATCTGGA for exon 10,5 0 -TACTGTG-TACTGTGCAAATGCATTGCAG for exon 15,5 0 -AGGTCAGTG-AGGTCAGTGCATGTCAAATCA for exon 16,5 0 -CTTTGGAGGT-CTTTGGAGGTGATGTTCTTTG and 5 0 -TTGGGAGAACAAAG-TGGGAGAACAAAGGATTGTG for exon 17,5 0 -ACTTAGAATC-ACTTAGAATCCATGGTGTGCA and 5 0 -AAAGCTCAGCTCTTC-AGCTCAGCTCTTCCATCAA for C6 exon 15. The purified PCR products (Multiscreen J plates; Millipore) were sequenced by the Dye terminator cycle sequencing method (Applied Biosystems).…”

Section: Genomic C7 Dna Sequencingmentioning

confidence: 99%

See 1 more Smart Citation

Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

et al. 2007

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Deficiencies in terminal complement components, including the component C7, are uncommon and associated with an increased risk of recurrent systemic neisserial infection. A total of 22 molecular defects have been reported in the C7 gene with both complete (C7Q0) and subtotal (C7SD) C7 deficiencies. In this study we report the molecular basis of nine new cases of C7 deficiencies that were characterized by exonspecific sequence analysis. Seven different C7 gene mutations were identified corresponding to small deletions (n=2), splice site changes (n=1) and single base pair substitutions leading to nonsense (n=1) or missense (n=3) mutations. Altogether, three changes of the C7 gene (G357R, R499S and 5 0 splice donor site of intron 16) account for half of the molecular defects which emphasize that a restricted number of molecular abnormalities are involved in this deficiency. We identified two patients with combined C7Q0/C7SD(R499S) and established the C7SD(R499S) frequency at about 1% in normal Caucasian population. We demonstrated that C7(R499S) mutant protein is retained in the endoplasmic reticulum whereas the wild-type C7 is located in the Golgi apparatus. Our results provide evidence that R499S represents a loss-of-function polymorphism of C7 due to a defective folding of the protein.

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“…Since these mutations lead to absence of C7 protein in the plasma, this C-terminal region is also likely to be crucial for C7 protein synthesis, secretion and/or stability [25].…”

Section: Discussionmentioning

confidence: 99%

Section: Genomic C7 Dna Sequencingmentioning

confidence: 99%

Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

et al. 2007

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“…This patient also had chronic otitis media that was only partially responsive to medical treatment; S. aureus and Bacteroides faecalis were cultured from middle ear pus (353). Complete deficiencies of C7 have been reported in several cases, and the molecular basis includes mutations at a 3Ј splice acceptor site in intron 1 (125), a mutation at a 5Ј splice donor site of intron 16, several point mutations (124,489), and deletion of part of the gene (326).…”

Section: Inherited Deficiencies Of Complement Activationmentioning

confidence: 99%

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

2010

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SUMMARY The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.

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“…This is almost certainly true of the Russian brothers with the exon 11 position 1561 C7SD defect that occurred without C6SD [75]. Nevertheless, the subject from Malta reported at this meeting with the exon 6 position 659 G 1 A transversion, and another as yet unknown C7SD defect, is C6 sufficient and was also shown to have low levels two different C7 allotypes in her circulation, despite the presence of circulating C6 and thus C5b6 [63,77].…”

Section: Deficiencies Of C7mentioning

confidence: 99%

“…Six defects, including the one responsible for C7SD in C6/C7SD and as isolated C7D, have been reported previously [65,75,76,78]. At this meeting a further 7 defects were described [63,77], making a total of 13 different known C7 defects. Most of these appear sporadic and have been only found in one or two independent chromosomes.…”

Section: Deficiencies Of C7mentioning

confidence: 99%

Reference Typing Report for Complement Components C6, C7 and C9 Including Mutations Leading to Deficiencies

Würzner

Witzel-Schlömp

Tokunaga

et al. 1998

Exp Clin Immunogenet

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The results of the present (VIIth Complement Genetics Workshop and Conference, Mainz, May 1998) and past reference typing workshops for the terminal complement components C6, C7 and C9 are compiled and discussed both on the protein level and on the DNA level. This report also focusses on the molecular bases of expressed and silent polymorphisms and reviews the molecular bases of subtotal and complete deficiencies of these proteins and their associations with protein and DNA markers. The results of the protein typing for C6 are published in the following paper of this issue.

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Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes

Cited by 21 publications

References 22 publications

Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

Reference Typing Report for Complement Components C6, C7 and C9 Including Mutations Leading to Deficiencies

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