Abstract
Properdin type I deficiency is characterised by complete absence of extracellular properdin, a positive regulator of the alternative pathway of complement activation. Properdin deficiency is associated with increased susceptibility to severe meningococcal disease. We have identified the genetic defect in 10 Dutch families. Six different mutations and one sequence polymorphism in the properdin gene were found. All amino acid substitutions were limited to conserved amino acids in exons 7 and 8 in contrast to the premature stops that were found in other exons. The missense mutations may alter the protein conformation in such a way that properdin will not be secreted and therefore catabolised intracellularly. The decreased properdin levels found in some healthy females carrying one mutated properdin gene were studied for X-inactivation. Most carriers with extreme low or high properdin levels showed preferential X-inactivation for the normal or mutated X chromosome, respectively. We observed some exceptions, suggesting additional regulation of properdin excretion apart from X-inactivation.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
van den Bogaard, R., Fijen, C., Schipper, M. et al. Molecular characterisation of 10 Dutch properdin type I deficient families: mutation analysis and X-inactivation studies. Eur J Hum Genet 8, 513ā518 (2000). https://doi.org/10.1038/sj.ejhg.5200496
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5200496
Keywords
This article is cited by
-
Human genetics of meningococcal infections
Human Genetics (2020)
-
The role of properdin in complement-mediated renal diseases: a new player in complement-inhibiting therapy?
Pediatric Nephrology (2019)
-
The X chromosome in immune functions: when a chromosome makes the difference
Nature Reviews Immunology (2010)
-
Genetische factoren van de gastheer in infecties met Neisseria meningitidis
Tijdschrift voor kindergeneeskunde (2004)