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. 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.

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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

References

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