title: Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency.
abstract: OBJECTIVE
  Homozygous C1q deficiency is an extremely rare condition and strongly associated with systemic lupus erythematosus. To assess and characterize C1q deficiency in an African-American lupus pedigree, C1q genomic region was evaluated in the lupus cases and family members.
  
  
  METHODS
  Genomic DNA from patient was obtained and C1q A, B and C gene cluster was sequenced using next generation sequencing method. The identified mutation was further confirmed by direct Sanger sequencing method in the patient and all blood relatives. C1q levels in serum were measured using sandwich ELISA method.
  
  
  RESULTS
  In an African-American patient with lupus and C1q deficiency, we identified and confirmed a novel homozygote start codon mutation in C1qA gene that changes amino acid methionine to arginine at position 1. The Met1Arg mutation prevents protein translation (Met1Arg). Mutation analyses of the patient's family members also revealed the Met1Arg homozygote mutation in her deceased brother who also had lupus with absence of total complement activity consistent with a recessive pattern of inheritance.
  
  
  CONCLUSIONS
  The identification of new mutation in C1qA gene that disrupts the start codon (ATG to AGG (Met1Arg)) has not been reported previously and it expands the knowledge and importance of the C1q gene in the pathogenesis of lupus especially in the high-risk African-American population.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. bahram.namjou@cchmc.org
authors.forename: B
authors.initials: B
authors.lastname: Namjou
authors.forename: M
authors.initials: M
authors.lastname: Keddache
authors.forename: D
authors.initials: D
authors.lastname: Fletcher
authors.forename: S
authors.initials: S
authors.lastname: Dillon
authors.forename: L
authors.initials: L
authors.lastname: Kottyan
authors.forename: G
authors.initials: G
authors.lastname: Wiley
authors.forename: P M
authors.initials: PM
authors.lastname: Gaffney
authors.forename: B E
authors.initials: BE
authors.lastname: Wakeland
authors.forename: C
authors.initials: C
authors.lastname: Liang
authors.forename: E K
authors.initials: EK
authors.lastname: Wakeland
authors.forename: R H
authors.initials: RH
authors.lastname: Scofield
authors.forename: K
authors.initials: K
authors.lastname: Kaufman
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D019943:Amino Acid Substitution; D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D055815:Young Adult
chemical_list: D018387:Codon, Initiator; D015922:Complement C1q