title: Identification of a novel non-coding mutation in C1qB in a Dutch child with C1q deficiency associated with recurrent infections.
abstract: BACKGROUND
  C1q deficiency is a rare genetic disorder that is strongly associated with development of systemic lupus erythematosus (SLE). Several mutations in the coding regions of the C1q genes have been described that result in stop-codons or other genetic abnormalities ultimately leading to C1q deficiency. Here we report on a Dutch boy suffering from recurrent infections with a complete C1q deficiency, without any SLE symptoms.
  
  
  METHODS
  The presence of C1q in serum was assessed using ELISA and hemolytic assay. By western blot we examined the different C1q chains in cell lysates. We identified the mutation using deep-sequencing. By qPCR we studied the mRNA expression of C1qA, C1qB and C1qC in the PBMCs of the patient.
  
  
  RESULTS
  Deep-sequencing revealed a homozygous mutation in the non-coding region of C1qB in the patient, whereas both parents were heterozygous. The mutation is located two nucleotides before the splice site of the second exon. In-silico analyses predict a complete abrogation of this natural splice site. Analyses of in vitro cultured cells from the patient revealed a lack of production of C1q and intracellular absence of C1qB in the presence of C1qA and C1qC peptides. Quantitative PCR analysis revealed total absence of C1qB mRNA, a reduced level of C1qA mRNA and normal levels of C1qC mRNA.
  
  
  CONCLUSIONS
  In this study we report a new mutation in the non-coding region of C1qB that is associated with C1q deficiency.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rosanne A
authors.initials: RA
authors.lastname: van Schaarenburg
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nina A
authors.initials: NA
authors.lastname: Daha
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Joris J M
authors.initials: JJ
authors.lastname: Schonkeren
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E W
authors.initials: EW
authors.lastname: Nivine Levarht
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: van Gijlswijk-Janssen
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Fina A S
authors.initials: FA
authors.lastname: Kurreeman
authors.affiliation: Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands; Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.affiliation: Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Carin A
authors.initials: CA
authors.lastname: Koelman
authors.affiliation: Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Margot R
authors.initials: MR
authors.lastname: Ernst-Kruis
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: L.A.Trouw@lumc.nl.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008297:Male; D009426:Netherlands; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012008:Recurrence; D017422:Sequence Analysis, DNA
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; D015922:Complement C1q
keywords: Autoimmunity; C1q deficiency; Complement; Infections; Mutation; Primary immunodeficiency