| 2. |
- Nordin Fredrikson, Gunilla, et al.
(författare)
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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
- 1998
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Ingår i: Human Immunology. - 0198-8859. ; 59:11, s. 713-719
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Nordin Fredrikson, Gunilla, et al.
(författare)
-
Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations
- 1998
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Ingår i: Journal of Clinical Immunology. - 0271-9142. ; 18:4, s. 272-282
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Tidskriftsartikel (refereegranskat)abstract
- Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316-->Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the properdin-deficient individuals produced properdin mRNA in a normal fashion. In type I deficiency no intracellular or secreted properdin was found, indicating rapid intracellular degradation. Monocytes from the males with type II deficiency expressed and secreted properdin normally. Properdin in sera with type II deficiency showed abnormal oligomerization with a relative decrease in properdin trimers and tetramers. Our findings suggest that the low concentration of circulating properdin in type II deficiency is caused by increased extracellular catabolism. Analysis of properdin expression by monocytes in a female carrier in the family with properdin deficiency type I provided direct evidence of lyonization at the cellular level.
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