Genetic Basis of Human Complement C8β Deficiency

Thomas Kaufmann, Gertrud Hänsch, Christian Rittner, Peter Späth, Francesco Tedesco, Peter M. Schneider

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The eighth component of human complement (C8) is a serum protein consisting of three chains (α, β, and γ) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the β subunit is non-covalently bound to the disulfide-linked α-γ subunit. Patients with C8β deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizes was observed in a C8β-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8β-deficient individuals was carried out. As a cause for C8β deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8β-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8β deficiency in the Caucasian population. In addition, two C8β-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined.

Original languageEnglish
Pages (from-to)4943-4947
Number of pages5
JournalJournal of Immunology
Volume150
Issue number11
Publication statusPublished - Jun 1 1993

Fingerprint

Complement C8
Medical Genetics
Exons
Alleles
Polymerase Chain Reaction
Introns
Chromosomes
Terminator Codon
Meningitis
Point Mutation
Disulfides
Restriction Fragment Length Polymorphisms
Sequence Analysis
Blood Proteins
Mutation
Infection
Serum
Population
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Kaufmann, T., Hänsch, G., Rittner, C., Späth, P., Tedesco, F., & Schneider, P. M. (1993). Genetic Basis of Human Complement C8β Deficiency. Journal of Immunology, 150(11), 4943-4947.

Genetic Basis of Human Complement C8β Deficiency. / Kaufmann, Thomas; Hänsch, Gertrud; Rittner, Christian; Späth, Peter; Tedesco, Francesco; Schneider, Peter M.

In: Journal of Immunology, Vol. 150, No. 11, 01.06.1993, p. 4943-4947.

Research output: Contribution to journalArticle

Kaufmann, T, Hänsch, G, Rittner, C, Späth, P, Tedesco, F & Schneider, PM 1993, 'Genetic Basis of Human Complement C8β Deficiency', Journal of Immunology, vol. 150, no. 11, pp. 4943-4947.
Kaufmann T, Hänsch G, Rittner C, Späth P, Tedesco F, Schneider PM. Genetic Basis of Human Complement C8β Deficiency. Journal of Immunology. 1993 Jun 1;150(11):4943-4947.
Kaufmann, Thomas ; Hänsch, Gertrud ; Rittner, Christian ; Späth, Peter ; Tedesco, Francesco ; Schneider, Peter M. / Genetic Basis of Human Complement C8β Deficiency. In: Journal of Immunology. 1993 ; Vol. 150, No. 11. pp. 4943-4947.
@article{e758ae489c30495dae42c3921afa49b2,
title = "Genetic Basis of Human Complement C8β Deficiency",
abstract = "The eighth component of human complement (C8) is a serum protein consisting of three chains (α, β, and γ) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the β subunit is non-covalently bound to the disulfide-linked α-γ subunit. Patients with C8β deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizes was observed in a C8β-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8β-deficient individuals was carried out. As a cause for C8β deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8β-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8β deficiency in the Caucasian population. In addition, two C8β-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined.",
author = "Thomas Kaufmann and Gertrud H{\"a}nsch and Christian Rittner and Peter Sp{\"a}th and Francesco Tedesco and Schneider, {Peter M.}",
year = "1993",
month = "6",
day = "1",
language = "English",
volume = "150",
pages = "4943--4947",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Genetic Basis of Human Complement C8β Deficiency

AU - Kaufmann, Thomas

AU - Hänsch, Gertrud

AU - Rittner, Christian

AU - Späth, Peter

AU - Tedesco, Francesco

AU - Schneider, Peter M.

PY - 1993/6/1

Y1 - 1993/6/1

N2 - The eighth component of human complement (C8) is a serum protein consisting of three chains (α, β, and γ) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the β subunit is non-covalently bound to the disulfide-linked α-γ subunit. Patients with C8β deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizes was observed in a C8β-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8β-deficient individuals was carried out. As a cause for C8β deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8β-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8β deficiency in the Caucasian population. In addition, two C8β-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined.

AB - The eighth component of human complement (C8) is a serum protein consisting of three chains (α, β, and γ) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the β subunit is non-covalently bound to the disulfide-linked α-γ subunit. Patients with C8β deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizes was observed in a C8β-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8β-deficient individuals was carried out. As a cause for C8β deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8β-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8β deficiency in the Caucasian population. In addition, two C8β-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined.

UR - http://www.scopus.com/inward/record.url?scp=0027241444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027241444&partnerID=8YFLogxK

M3 - Article

C2 - 8098723

AN - SCOPUS:0027241444

VL - 150

SP - 4943

EP - 4947

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -