Nonsense mutation in exon 4 of human complement C9 gene is the major cause of Japanese complement C9 deficiency
1Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan. kirari@mailserver.med.kyushu-u.ac.jp
Insights
Ninth component of complement (C9) deficiency is common in Japan due to a specific mutation. This genetic defect, identified in patients with meningococcal meningitis, is linked to a common molecular cause in the Japanese population.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Deficiency of the ninth component of human complement (C9) is prevalent in Japan, unlike other regions.
- C9 deficiency is associated with an increased risk of meningococcal meningitis.
Purpose of the Study:
- To investigate the molecular basis of C9 deficiency in Japanese patients.
- To identify the specific genetic mutation responsible for C9 deficiency in the studied cohort.
Main Methods:
- Direct sequencing of C9 cDNA and DNA was performed on four Japanese patients.
- Allele-specific polymerase chain reaction (PCR) was used to genotype patients and their parents.
Main Results:
- A nonsense substitution (CGA-->TGA) at codon 95 in exon 4 of the C9 gene was identified in all four patients.
- Patients were homozygous for this mutation, and parents were heterozygous, confirming its inheritance pattern.
- This specific mutation is likely the predominant cause of C9 deficiency in Japan.
Conclusions:
- A common mutation in the C9 gene at codon 95 is responsible for the majority of C9 deficiency cases in Japan.
- Understanding the genetic basis of C9 deficiency aids in diagnosing and managing related infections.
Abstract:
Deficiency of the ninth component of human complement (C9) is the most common complement deficiency in Japan but is rare in other countries. We studied the molecular basis of C9 deficiency in four Japanese C9-deficient patients who had suffered from meningococcal meningitis. Direct sequencing of amplified C9 cDNA and DNA revealed a nonsense substitution (CGA-->TGA) at codon 95 in exon 4 in the four C9-deficient individuals. An allele-specific polymerase chain reaction system designed to detect exclusively only one of the normal and mutant alleles indicated that all the four patients were homozygous for the mutation in exon 4 and that the parents of patient 2 were heterozygous. The common mutation at codon 95 in exon 4 might be responsible for most Japanese C9 deficiency.
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