The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene; a new aspect of pathogenesis for C3 deficiency.
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.
Kida
Miyuki
M
Department of Pediatrics, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido, Japan.
Fujioka
Hirotaka
H
Kosaka
Yoshiyuki
Y
Hayashi
Kouhei
K
Sakiyama
Yukio
Y
Ariga
Tadashi
T
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
D003176:Complement C3