Molecular characterization of two novel cases of complete complement inhibitor Factor I deficiency.

Izabela Nita, Ferah Genel, Sara Nilsson, Joanne Smart, Lennart Truedsson, Sharon Choo, Anna Blom

Research output: Contribution to journalArticlepeer-review

12 Citations (SciVal)
103 Downloads (Pure)


Factor I (FI) is the major complement inhibitor that degrades activated complement components C3b and C4b in the presence of specific cofactors. Complete FI deficiency results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation. In this study we describe two unrelated patients with complete FI deficiency and undetectable alternative complement pathway activity. Both patients had experienced recurrent infections and arthralgia/arthritis. In one patient, analysis of genomic DNA revealed deletion of two adenine nucleotides in exon 2 of the CFI gene (c.133-134delAA), causing a frame shift and premature STOP codon/termination in the FIMAC (FI-membrane attack complex) domain (p.K45SfsX11). The other patient carried an A>T substitution in exon 6 (c.866A>T) encoding the LDLr2 (low density lipoprotein receptor) domain (p.D289V), resulting in an aspartic acid to valine change. Both patients were homozygous for the mutations while their healthy parents were heterozygous carriers. The mutations were introduced into recombinant FI, causing lack of FI expression and secretion upon transient transfection. Mutation p.K45SfsX11 theoretically allows expression of a 55 amino acid fragment of FI that lacks the serine protease domain, preventing proteolytic activity. In contrast, aspartic acid D289 is crucial for folding of FI. This report describes the molecular and functional consequences of two novel mutations of FI, providing a unique insight into the pathogenesis of complete FI deficiency in these patients.
Original languageEnglish
Pages (from-to)1068-1072
JournalMolecular Immunology
Issue number8
Publication statusPublished - 2011

Subject classification (UKÄ)

  • Immunology in the medical area


Dive into the research topics of 'Molecular characterization of two novel cases of complete complement inhibitor Factor I deficiency.'. Together they form a unique fingerprint.

Cite this