title: Age-dependent association of human mannose-binding lectin mutations with susceptibility to invasive meningococcal disease in childhood.
abstract: BACKGROUND
  Mannose-binding lectin (MBL) is an important factor of the innate immune system, and MBL-initiated complement activation is an important early defense mechanism against various bacterial infections, including invasive meningococcal disease.
  
  
  METHODS
  In a pediatric cohort (ages 2-215 months) with invasive meningococcal disease, we investigated the overall and age-stratified frequency of 3 MBL exon 1 variations (C154T, G161A, G170A), previously shown to result in markedly decreased MBL plasma concentrations, by allele specific fluorescent hybridization probe real-time PCR assays and direct sequencing. Healthy age-matched volunteers with the same ethnic background and no history of meningococcal disease served as a control group.
  
  
  RESULTS
  The overall frequency of a MBL exon 1 variant genotype was significantly higher in patients than in controls (31.8% vs. 8.2%, P < 0.001). In the patient group with disease onset less than 24 months of age, the prevalence of MBL structural variant genotype was further increased (39.3%; P < 0.001) and most pronounced in children with disease onset less than 12 months of age (57.1%; P < 0.001) when compared with healthy controls. Analysis of clinical severity and outcome revealed no significant difference between patients with wild-type and mutant alleles.
  
  
  CONCLUSIONS
  Our data suggest that MBL exon 1 structural variants are significantly associated with susceptibility to childhood meningococcal disease in an age-dependent manner.
authors.affiliation: Children's Hospital, Johannes Gutenberg-University, Mainz, Germany. jorg.faber@childrens.harvard.edu
authors.forename: Joerg
authors.initials: J
authors.lastname: Faber
authors.forename: Therese
authors.initials: T
authors.lastname: Schuessler
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.forename: Craig
authors.initials: C
authors.lastname: Murdoch
authors.forename: Werner
authors.initials: W
authors.lastname: Zenz
authors.forename: Pirmin
authors.initials: P
authors.lastname: Habermehl
authors.forename: Claudius U
authors.initials: CU
authors.lastname: Meyer
authors.forename: Bernhard U
authors.initials: BU
authors.lastname: Zabel
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmitt
authors.forename: Fred
authors.initials: F
authors.lastname: Zepp
authors.forename: Markus
authors.initials: M
authors.lastname: Knuf
mesh_terms: D000293:Adolescent; D000375:Aging / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008589:Meningococcal Infections / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D015995:Prevalence
chemical_list: D037601:Mannose-Binding Lectin