title: Common silent mutations in all types of hereditary complement C1q deficiencies.
abstract: Hereditary complete deficiency of complement component C1q is a rare genetic disorder that is associated with severe recurrent infections and a high prevalence of lupus-erythematosus-like symptoms. In the past, several single nucleotide polymorphisms have been identified in all three genes coding for the C1q A, B, and C chains. These point mutations which either lead to termination codons, frameshift, or amino acid exchanges were thought to be responsible for these defects as no other nonsense or missense mutations were found. As a result of the aberrations, either a nonfunctional C1q antigen is present or no C1q protein is detectable in the patients' sera. Screening 46 individuals from seven families with different forms of C1q deficiencies identified a homologous silent mutation at position Gly70 (GGG > GGA) of the C1q A gene of all 11 C1q-deficient patients. A high number of family members that were heterozygous for the coding mutations carried the silent mutation in the homozygous (18%) or heterozygous (36%) state. In addition to the Gly70 mutation in the A gene, another homozygous silent mutation (C gene at position Pro14, CCT >CCC) was detected in all C1q-deficient patients.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Germany. fpetry@mail.uni-mainz.de
authors.forename: Franz
authors.initials: F
authors.lastname: Petry
authors.forename: Michael
authors.initials: M
authors.lastname: Loos
mesh_terms: D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D015922:Complement C1q