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B Uring-Lambert

Publications and source records attributed to B Uring-Lambert.

31 records · Page 2Linked to original sources
PubMed1990

C4 reference typing report.

Human C4 is most polymorphic at the protein level, distinction between allotypes of the C4A and C4B proteins resting on electrophoretic migration patterns and difference in hemolytic activity. The aim of the C4 reference typing has been the definition of reference variants, the assignment of rare variants, and the investigation of duplicated, deleted, or non-expressed and hybrid genes. Samples from 136 individuals, predominantly with known segregation, from 16 laboratories were investigated by standard electrophoretic techniques, for their relative hemolytic activity, reactivity with monoclonal antibodies and Rg/Ch reagents, alpha-, and beta-chain types, relative electrophoretic migration distance, as well as the C4/21-OH-TaqI RFLPs. The results were evaluated in three groups; they consisted in the definition of the eight most common C4 alleles, and the ten Rg/Ch standard phenotypes in group I. In group II twelve C4A and fourteen C4B duplications among 96 complotypes, as well as eighteen deleted/non-expressed C4A and twenty-two C4B alleles, and hybrid alleles were seen by correlation of lytic activity, electrophoretic mobility, and monoclonal and/or Rg/Ch reactivity. Group III consisted of the newly defined allotypes A 8, A 7, A 58, A 55, A 45, B 45, B 35, and B 22, furthermore of alleles subdividing the A 1/A 91, and the B 13/B 12/B 11 regions. The reference typing has allowed reclassification of the majority of described C4 allotypes and resulted in a revision of the C4 nomenclature.

Blood Grouping and Crossmatching↗
PubMed1989

Molecular basis of complete C4 deficiency. A study of three patients.

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes, C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes and is also remarkable by the high frequency of the null alleles, C4A*Q0 and C4B*Q0. Complete C4 deficiency is exceptional because this condition appears only in homozygotes for the very rare double-null haplotype C4AQ0,BQ0. This condition in most cases gives rise to systemic lupus erythematosus and an increased susceptibility to infections. The molecular basis for complete C4 deficiency has not yet been established. Therefore we studied the DNA of three previously described C4 deficient patients belonging to unrelated families by restriction fragment length polymorphism analysis using C4 and 21-OH probes. These studies revealed a deletion of the C4B and 21-OHA genes in two patients and no deletion at all in the third patient. Therefore, complete C4 deficiency as a result of homozygosity for the C4AQ0, BQ0 haplotype is not a consequence of a deletion of the C4 genes. The molecular basis of this genetic abnormality is certainly very complex and may vary also from one case to another.

Alleles↗
PubMed1989

Rearrangements and point mutations of P450c21 genes are distinguished by five restriction endonuclease haplotypes identified by a new probing strategy in 57 families with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is caused by disorders of the P450c21B gene, which, with the P450c21A pseudogene, lies in the HLA locus on chromosome 6. The near identity of nucleotide sequences and endonuclease cleavage sites in these A and B loci makes genetic analysis of this disease difficult. We used a genomic DNA probe that detects the P450c21 genes (A pseudogene, 3.2 kb; B gene, 3.7 kb in Taq I digests) and the 3' flanking DNA not detected with cDNA probes (A pseudogene, 2.4 kb; B gene, 2.5 kb) to examine Southern blots of genomic DNA from 68 patients and 165 unaffected family members in 57 families with CAH. Of 116 CAH-bearing chromosomes, 114 could be sorted into five easily distinguished haplotypes based on blots of DNA digested with Taq I and Bgl II. Haplotype I (76 of 116, 65.6%) was indistinguishable from normal and therefore bore very small lesions, presumably point mutations. Haplotype II (4 of 116, 3.4%) and haplotype III (8 of 116, 6.9%) had deletions and duplications of the P450c21A pseudogene but had structurally intact P450c21B genes presumably bearing point mutations; point mutation thus was the genetic defect in 88 of 116 chromosomes (75.9%). Haplotypes IV and V lack the 3.7-kb Taq I band normally associated with the P450c21B gene. Haplotype IV (13 of 116, 11.2%) retains all other bands, indicating that the P450c21B gene has undergone a gene conversion event, so that it is now also associated with a 3.2-kb band. Haplotype V (13 of 116, 11.2%) lacks the 2.4-kb Taq I fragment and the 12-kb Bgl II fragments normally associated with the P450c21A pseudogene, as well as lacking the 3.7-kb Taq I fragment, indicating deletion of approximately 30 kb of DNA, resulting in a single hybrid P450c21A/B gene. Most (114 of 116, 98%) CAH alleles thus can easily be classified with this new probing strategy, eliminating many ambiguities resulting from probing with cDNA.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Familial properdin deficiency associated with chronic discoid lupus erythematosus.

A large family comprised of 18 members is described. Four male members are properdin-deficient, all are healthy bar the index patient who presented with chronic discoid lupus erythematosus. Serum from properdin-deficient males had a reduced ability to lyse rabbit erythrocytes via the alternative pathway or solubilize pre-formed immune complexes. Addition of purified properdin restored these activities. Classical pathway activity was normal. Definite, probable and possible female carriers had normal classical and alternative pathway activities.

Family↗
PubMed1988

Antigenic determinants expressed by human C4 allotypes; a study of 325 families provides evidence for the structural antigenic model.

The antigenic determinants of human C4 have been defined by human IgG antisera, Rodgers (Rg) and Chido (Ch), in hemagglutination-inhibition assays (HAI). Eight (2 Rg and 6 Ch) are of high frequency, greater than 90%, and 1, WH, is of low frequency, 15%. The phenotypic combinations are complex; generally, C4A expresses Rg, and C4B has Ch, but reverse antigenicities have been established both by HAI and by sequence data of selected C4 allotypes. A study of 325 families provides data on the antigenic expression of each C4 allotype and demonstrates strong associations. A structural model for the antigenic determinants of C4 proteins has been proposed and is completely supported by the family material. Of the 16 possible antigenic combinations for C4 proteins, only 3 are undetected. A new Ch combination has been recorded in two French families. The reported sequence variation within the C4d region can account for the antigenic determinants but leaves the location of electrophoretic variation in C4 still unclear.

Blood Group Antigens↗
PubMed1988

Polymorphism of MHC class III genes: definition of restriction fragment linkage groups and evidence for frequent deletions and duplications.

The loci for the complement proteins BF and C2 and the two loci for C4 are closely linked to one another, as are the duplicated steroid 21 hydroxylase (21-OHase) genes to the C4A and C4B loci. The alleles of these four loci occur in specific combinations termed "complotypes". We have studied the gene frequencies of their different products in the Lebanese population and compared these values with those found in other populations. We observed a novel complotype (S B 4 6) in one family and a complotype with a so far undescribed variant of the C4A locus. Using several restriction fragment length polymorphisms (RFLPs), we have defined restriction fragment linkage groups. The combined use of C4 and 21-OHase probes allowed us to detect different types of deletions and duplications at these loci in the Lebanese population.

Chromosome Deletion↗
PubMed1987

Heterogeneity in the structural basis of the human complement C4A null allele (C4A Q0) as revealed by HindIII restriction fragment length polymorphism analysis.

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes. C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes, 21-OHA and 21-OHB, and is also remarkable in the high frequency of the 'null' alleles, C4A Q0 and C4B Q0. The molecular basis for the C4A Q0 allele was studied in 26 families through restriction fragment length polymorphism (RFLP) analysis with C4 and 21-OH cDNA probes after digestion of the DNA with the endonuclease HindIII. The individuals expressing the extended haplotype HLA-A1 (of A2) Cw7 B8 C2C BfS C4AQ0B1 DR3 have a large deletion taking off the C4A and 21-OHA genes.

Alleles↗
PubMed1987

The study of a French family with two duplicated C4A haplotypes.

The finding of two duplicated C4A haplotypes in a normal French family led to a detailed study of their C4 polymorphism. The father had an extremely rare A*6A*11, B*QO haplotype inherited by all of his children and the mother had the more common A*3A*2, B*QO haplotype. Two HLA identical daughters only have four C4A alleles. The father's A11 allotype expresses Ch:1 (Chido) rather than Rg:1 (Rodgers) and represents a new Ch phenotype Ch:1,-2,-3,-4,-5,-6. In order to clarify the genetic background in this unusual family, DNA studies of restriction fragment length polymorphisms (RFLPs) were undertaken. The father's rare haplotype, which expresses two C4A allotypes, results from a long and a short C4 gene normally associated with the A*6, B*1 that also exhibits the Bg/II RFLP. As it travels in an extended MHC haplotype HLA A2, B57(17), C2*C, BF*S, DR7 that is most frequently associated with A*6, B*1, we postulate that the short C4B has been converted in the alpha chain region to a C4A gene which produces a C4A protein. This report of a short C4A gene is the first example in the complex polymorphism of C4.

Alleles↗
PubMed1985

Detection of the genetic polymorphism of human C2 (native protein and C2a fragment) by immunoblotting after polyacrylamide gel isoelectric focusing.

The polymorphism of the second component of human complement (C2) was studied by means of isoelectric focusing in polyacrylamide gels followed by immunoblotting with a specific antihuman C2 antibody. The polymorphism was studied in native C2 and in the C2a fragment obtained by activation of the classical pathway with heat-aggregated human IgG. Serum samples previously typed with the hemolytic overlay technique were analyzed. They comprised samples of homozygous C2*C, C2*B, C2*Q0, heterozygous C2*BC and C2*CQ0 individuals. The patterns obtained by immunoblotting corresponded to those obtained by the hemolytic overlay technique. As expected, the homozygous C2*Q0 sample (complement C2 deficiency) did not show any band pattern. The C2a fragment presented also a polymorphic variation which correlated exactly with the native C2 polymorphism. It appears thus that the polymorphic site of the C2 protein is carried by the C2a fragment for the C2*C and C2*B variants. In addition, this method is easier to perform than the common hemolytic overlay technique and the rare C2-deficient serum is not needed.

Complement C2↗