Genetic basis of human complement C8α-γ deficiency

Takeshi Kojima, Takahiko Horiuchi, Hiroaki Nishizaka, Yasuo Fukumori, Tetsuki Amano, Kohei Nagasawa, Yoshiyuki Niho, Kenshi Hayashi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Deficiency of the α-γ subunit of the eighth component of complement (C8α-γD) is frequently associated with recurrent neisserial infections, especially meningitis caused by Neisseria meningitidis. We here report the molecular basis of C8α-γD in two unrelated Japanese subjects. Screening all 11 exons of the C8α gene and all 7 exons of the C8γ gene and their boundaries by exon-specific PCR/single-strand conformation polymorphism demonstrated aberrant single-stranded DNA fragments in exon 2 of C8α gene in case 1 and in exons 2 and 9 of C8α gene in case 2. Nucleotide sequencing of the amplified DNA fragments in case 1 revealed a homozygous single-point mutation at the second exon-intron boundary, inactivating the universally conserved 5' splice site consensus sequence of the second intron (IVS2+IG→T). Case 2 was a compound heterozygote for the splice junction mutation, IVS2+IG→T, and a nonsense mutation at Arg394 (R394x). R394X was caused by a C to T transition at nucleotide 1407, the first nucleotide of the codon CGA for Arg394, leading to a stop codon TGA. No mutations were detected in the C8γ gene by our method. Our results indicate that the pathogenesis of C8α-γD might be caused by heterogeneous molecular defects in the C8α gene.

Original languageEnglish
Pages (from-to)3762-3766
Number of pages5
JournalJournal of Immunology
Volume161
Issue number7
Publication statusPublished - Oct 1 1998

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Complement C8
Medical Genetics
Exons
Genes
Nucleotides
Introns
Complement Factor D
RNA Splice Sites
Mutation
Neisseria meningitidis
Terminator Codon
Nonsense Codon
Single-Stranded DNA
Consensus Sequence
Heterozygote
DNA Sequence Analysis
Meningitis
Point Mutation
Codon
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kojima, T., Horiuchi, T., Nishizaka, H., Fukumori, Y., Amano, T., Nagasawa, K., ... Hayashi, K. (1998). Genetic basis of human complement C8α-γ deficiency. Journal of Immunology, 161(7), 3762-3766.

Genetic basis of human complement C8α-γ deficiency. / Kojima, Takeshi; Horiuchi, Takahiko; Nishizaka, Hiroaki; Fukumori, Yasuo; Amano, Tetsuki; Nagasawa, Kohei; Niho, Yoshiyuki; Hayashi, Kenshi.

In: Journal of Immunology, Vol. 161, No. 7, 01.10.1998, p. 3762-3766.

Research output: Contribution to journalArticle

Kojima, T, Horiuchi, T, Nishizaka, H, Fukumori, Y, Amano, T, Nagasawa, K, Niho, Y & Hayashi, K 1998, 'Genetic basis of human complement C8α-γ deficiency', Journal of Immunology, vol. 161, no. 7, pp. 3762-3766.
Kojima T, Horiuchi T, Nishizaka H, Fukumori Y, Amano T, Nagasawa K et al. Genetic basis of human complement C8α-γ deficiency. Journal of Immunology. 1998 Oct 1;161(7):3762-3766.
Kojima, Takeshi ; Horiuchi, Takahiko ; Nishizaka, Hiroaki ; Fukumori, Yasuo ; Amano, Tetsuki ; Nagasawa, Kohei ; Niho, Yoshiyuki ; Hayashi, Kenshi. / Genetic basis of human complement C8α-γ deficiency. In: Journal of Immunology. 1998 ; Vol. 161, No. 7. pp. 3762-3766.
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