title: The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene; a new aspect of pathogenesis for C3 deficiency.
abstract: The complement system is an ancient cascade system that has a major role in innate and adaptive immunity. Component C3 is central to the three complement pathways. Hereditary compliment 3 (C3) deficiency characterized by severe recurrent infections and immune complex disorders is extremely rare disease. Since 1972, inherited C3 deficiency has been described in many families representing a variety of national origins; however, only 8 families of these cases have been identified their genetic defects. Interestingly, all except one (incomplete analysis) were shown to harbor homozygous C3 gene mutations. Previously we proposed a hypothesis, based on the unique process of C3 synthesis; C3 deficiency is not inherited as a simple autosomal recessive trait. Here, we report the first confirmed case with C3 deficiency caused by compound heterozygous mutations. They were a novel one base insertion (3176insT) in exon 24 which is predicted to result in a frameshift and a premature downstream stop codon (K1105X) in exon 26, and a nonsense mutation of C3303G (Y1081X) in exon 26 which was previously reported as homozygous mutations. This confirmed case suggests that our proposed hypothesis has prospects of a new aspect of pathogenesis for C3 deficiency.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kida
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Fujioka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.forename: Kouhei
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
mesh_terms: D002675:Child, Preschool; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D003176:Complement C3