title: C1q deficiency in an Inuit family: identification of a new class of C1q disease-causing mutations.
abstract: C1q deficiency is a rare condition associated with a systemic lupus erythematosus (SLE)-like syndrome and recurrent infections. Here we present the molecular basis behind C1q deficiency in three sisters of Inuit origin. Initial examination for complement deficiency showed no function of the classical complement activation pathway in the patients; the lectin and alternative pathways were intact. No C1q or low molecular weight C1q was detected in sera and no anti-C1q autoantibodies were found. Sequencing of the C1q genes revealed a novel missense mutation (Gly-Arg) in codon 217 of the B chain. All sisters were homozygous for the mutation: both parents were heterozygous. None of 100 healthy controls carried the mutation. Our findings define a third class of molecular mechanisms behind C1q deficiency, where missense mutations cause a lack of detectable C1q-antigen in serum.
authors.affiliation: Dept. of Clinical Immunology sect. 7631, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Denmark. hanne.marquart@rh.hosp.dk <hanne.marquart@rh.hosp.dk>
authors.forename: Hanne Vibeke
authors.initials: HV
authors.lastname: Marquart
authors.forename: Lone
authors.initials: L
authors.lastname: Schejbel
authors.forename: Anders
authors.initials: A
authors.lastname: Sjoholm
authors.forename: Ulla
authors.initials: U
authors.lastname: Martensson
authors.forename: Susan
authors.initials: S
authors.lastname: Nielsen
authors.forename: Anders
authors.initials: A
authors.lastname: Koch
authors.forename: Arne
authors.initials: A
authors.lastname: Svejgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000293:Adolescent; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics*; D015941:Complement Hemolytic Activity Assay; D003241:Consanguinity; D005260:Female; D005998:Glycine / Q000235:genetics; D006116:Greenland; D006720:Homozygote; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D035781:Siblings
chemical_list: D015922:Complement C1q; D001120:Arginine; D005998:Glycine