C1q deficiency in an Inuit family: Identification of a new class of C1q disease-causing mutations

• Published in: Clinical Immunology
• Main Authors: Marquart, Hanne Vibeke, Schejbel, Lone, Sjöholm, Anders, Mårtensson, Ulla, Nielsen, Susan, Koch, Anders, Svejgaard, Arne, Garred, Peter
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2007
• Subjects: Immunology in the medical area; autoimmunity; primary immunodeficiency; mutation; classical pathway; infections; SLE; C1q deficiency; complement; Three Sisters; inuit
• Online Access: https://lup.lub.lu.se/record/645857; https://doi.org/10.1016/j.clim.2007.03.547

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 tow molecular weight Clq 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. (c) 2007 Elsevier Inc. ALL rights reserved.