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Published on: January 29, 2014
Molecular analysis of hereditary deficiency of the third component of complement (C3) in two sisters
W Matsuyama1, M Nakagawa, H Takashima
1Third Department of Internal Medicine, Kagoshima University Faculty of Medicine.
Insights
Hereditary deficiency of the third complement component (C3) was observed in two sisters who developed lupus-like symptoms. A novel stop codon mutation in the C3 gene was identified as the cause.
Area of Science:
- Immunogenetics
- Complement System Biology
- Autoimmune Disease Pathogenesis
Background:
- Hereditary complement deficiencies predispose individuals to autoimmune diseases.
- The third complement component (C3) is crucial for both innate and adaptive immunity.
- Systemic lupus erythematosus (SLE)-like symptoms are associated with certain complement deficiencies.
Observation:
- Two sisters presented with SLE-like symptoms and undetectable serum C3 levels.
- Genetic analysis revealed a homozygous C3303G (Tyr1081Stop) mutation in the affected sisters.
- Family members with heterozygous mutations exhibited reduced C3 levels.
Findings:
- The identified C3 mutation resulted in a premature stop codon, leading to a lack of detectable C3 protein.
- Messenger RNA (mRNA) for C3 was present, indicating a post-transcriptional defect.
- This is the first documented case of C3 deficiency caused by a stop codon mutation.
Implications:
- This study highlights the critical role of C3 in immune system regulation.
- Understanding the genetic basis of C3 deficiency can aid in diagnosing and managing autoimmune conditions.
- The findings provide insights into complement-mediated autoimmunity and potential therapeutic targets.
Abstract:
We report two sisters with hereditary deficiency of the third complement component (C3) and a homozygous mutation at C3303G (Tyr1081Stop) of the gene. They developed systemic lupus erythematosus-like symptoms during adolescence. Their C3 were not detected in serum immunochemically. Their mother and a brother had half of the normal C3 levels and a heterozygous mutation in the same position. Western blot analysis of murine L-cells transfected with the mutant C3 cDNA showed no C3 protein, however mRNA was detectable using reverse-transcriptase polymerase chain reaction. To the best of our knowledge, this is the first report of C3 deficiency due to a stop codon in the gene.
