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Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop codon

Nordin Fredrikson, Gunilla LU ; Gullstrand, Birgitta LU ; Schneider, P M; Witzel-Schlomp, K; Sjöholm, Anders LU ; Alper, C A; Awdeh, Z and Truedsson, Lennart LU (1998) In Human Immunology 59(11). p.713-719
Abstract
The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4... (More)
The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Immunology
volume
59
issue
11
pages
713 - 719
publisher
Elsevier
external identifiers
  • pmid:9796739
  • scopus:0031717781
ISSN
0198-8859
DOI
10.1016/S0198-8859(98)00068-8
language
English
LU publication?
yes
id
8d3fa1ee-eb62-482d-a1f0-14625cb09760 (old id 1113296)
date added to LUP
2008-07-14 16:13:18
date last changed
2017-03-12 03:34:45
@article{8d3fa1ee-eb62-482d-a1f0-14625cb09760,
  abstract     = {The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency.},
  author       = {Nordin Fredrikson, Gunilla and Gullstrand, Birgitta and Schneider, P M and Witzel-Schlomp, K and Sjöholm, Anders and Alper, C A and Awdeh, Z and Truedsson, Lennart},
  issn         = {0198-8859},
  language     = {eng},
  number       = {11},
  pages        = {713--719},
  publisher    = {Elsevier},
  series       = {Human Immunology},
  title        = {Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop codon},
  url          = {http://dx.doi.org/10.1016/S0198-8859(98)00068-8},
  volume       = {59},
  year         = {1998},
}