Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jun 18:7:42.
doi: 10.1186/1750-1172-7-42.

Complement factor I deficiency: a not so rare immune defect: characterization of new mutations and the first large gene deletion

María Alba-Domínguez  1 , Alberto López-Lera, Sofía Garrido, Pilar Nozal, Ignacio González-Granado, Josefa Melero, Pere Soler-Palacín, Carmen Cámara, Margarita López-Trascasa
Affiliations

Complement factor I deficiency: a not so rare immune defect: characterization of new mutations and the first large gene deletion

María Alba-Domínguez et al. Orphanet J Rare Dis. .

Abstract

Background: Complement Factor I (CFI) is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide.

Patients and methods: We have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included.

Results: Molecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1.

Conclusion: CFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Pedigrees and complement studies.A) Pedigrees of the families with CFI deficiency. Black symbols represent complete deficient of CFI and half-filled symbols indicate partial deficiency. B) Western blot analysis of CFI in serum samples. C) Complement profiles: measurement of C3, C4, CFB, CFH, CFI, C3NeF and CFHA plasma levels. Abbreviations used: NEG, negative. ND, not determined. CFB, Complement Factor B. CFH, Complement Factor H. CFI, Complement Factor I. C3NeF, C3 Nephritic Factor. CFHA, Complement Factor H auto antibodies.
Figure 2
Figure 2
Long range PCR. XL-PCR of a genomic fragment spanning approximately 8Kb. Patient III.1, his mother (III.2) and brother (III.4) are heterozygous for the exon 2 deletion. His father (III.3) does not carry the deletion.
Figure 3
Figure 3
Schematic model of the CFI protein and gene. The protein domains, exon/intron gene structure and the mutations found in our series are depicted.
Figure 4
Figure 4
Additional studies for a patient with low C3 (20-30% of normal expression) and normal C4: Alternative pathway of complement activation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Botto M, Kirschfink M, Macor P, Pickering MC, Würzner R, Tedesco F. Complement in human diseases: Lessons from complement deficiencies. Mol Immunol. 2009;46(14):2774–2783. doi: 10.1016/j.molimm.2009.04.029. - DOI - PubMed
    1. Degn SE, Jensenius JC, Thiel S. Disease-causing mutations in genes of the complement system. Am J Hum Genet. 2011;88(6):689–705. doi: 10.1016/j.ajhg.2011.05.011. - DOI - PMC - PubMed
    1. Sullivan KE, Winkelstein JA. In: Genetically Determined Deficiencies of the Complement System. 2. Ochs HD, Smith CIE, Puck JM, editor. Oxford University Press, New York; 2007. Primary Immunodeficiency Diseases: a molecular and genetic approach; pp. 589–608.
    1. Roversi P, Johnson S, Caesar JJ, McLean F, Leath KJ, Tsiftsoglou SA, Morgan BP, Harris CL, Sim RB, Lea SM. Structural basis for complement factor I control and its disease-associated sequence polymorphisms. Proc Natl Acad Sci U S A. 2011;108(31):12839–12844. doi: 10.1073/pnas.1102167108. - DOI - PMC - PubMed
    1. Nilsson SC, Sim RB, Lea SM, Fremeaux-Bacchi V, Blom AM. Complement Factor I in health and disease. Mol Immunol. 2011;48(14):1611–1620. doi: 10.1016/j.molimm.2011.04.004. - DOI - PubMed

Publication types

MeSH terms

Supplementary concepts