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A non-sense mutation at Arg95 is predominant in complement 9 deficiency in Japanese
T Horiuchi1, H Nishizaka, T Kojima
1First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. horiuchi@intmed1.med.kyushu-u.ac.jp
Journal of Immunology (Baltimore, Md. : 1950)
|May 7, 1998
Summary
Deficiency of the ninth component of complement (C9D) is common in Japan. A novel mutation, R95X, was identified as the primary cause of C9D in most Japanese subjects, increasing meningococcal meningitis risk.
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Genetics
Background:
- Deficiency of the ninth component of complement (C9D) is a prevalent genetic disorder in Japan, affecting 1 in 1000 individuals.
- While C9D individuals are typically asymptomatic, they exhibit a significantly elevated risk of developing meningococcal meningitis.
Observation:
- This study investigated the molecular basis of C9D in 10 unrelated Japanese subjects.
- Analysis of C9 gene exons 2-11 using PCR/single-strand conformation polymorphism revealed abnormalities in exon 4 in all C9D subjects.
- Direct sequencing identified a novel C to T transition (R95X) in exon 4 in 8 out of 10 subjects, resulting in a premature stop codon.
Findings:
- The novel R95X mutation was found to be homozygous in most Japanese C9D cases studied.
- Heterozygous R95X mutations were observed in two cases, with one also carrying a second mutation (C507Y).
- The genetic basis for C9D in one subject remains undetermined, indicating potential allelic heterogeneity.
Implications:
- The R95X mutation is identified as the predominant cause of C9D in the Japanese population.
- Understanding the molecular basis of C9D is crucial for assessing meningococcal meningitis risk in affected individuals.
- Further research may elucidate the genetic defect in remaining C9D cases and explore genotype-phenotype correlations.