ABSTRACT
The authors describe a newly identified beta0-thalassaemic mutation found in two subjects from two generations of a Slovak family. The beta0-thalassaemic allele developed by insertion of one nucleotide (+G, CD 7/8) into the first exon of the beta-globin gene. The mutation causes a shift of the open globin reading frame which leads to the development of a terminal codon in codon 22. The thalassaemic allele is associated with the mediterranean haplotype IX. The mutation has in both heterozygotes the phenotype of beta0-thalassaemia minor with a slightly elevated level of HbF.
Subject(s)
Frameshift Mutation , Globins/genetics , beta-Thalassemia/genetics , Alleles , Codon, Terminator/genetics , Exons/genetics , Female , Haplotypes , Heterozygote , Humans , Male , Middle Aged , Pedigree , Phenotype , Sequence Analysis, DNAABSTRACT
The unstable haemoglobin variant Ana (alpha 2 beta 2 88 (F4) Leu-Pro) was identified to cause haemolysis in a 10-year-old Slovak girl. She was followed for haemolytic anaemia symptoms since two years of age. Clinical signs are hepatosplenomegaly and moderate haemolytic anaemia not requiring blood transfusions. It is the first case of an unstable haemoglobinopathy found in Slovak Republic as far as we know. Hypothesis of 'de novo' origin of the mutation in the propositus is supported by the parents' and brother's laboratory findings.
Subject(s)
Anemia, Hemolytic, Congenital/blood , Hemoglobins, Abnormal/genetics , Anemia, Hemolytic, Congenital/genetics , Base Sequence , Child , Female , Humans , Male , Point MutationABSTRACT
In four unrelated families of Czech and Slovak origin two nonsense dominant beta-thalassaemic alleles (CD 121 (G-T); CD 112 (T-A)) and in one family simple substitution in codon 115 (GCC-GAC) or alpha 2 beta 2 115 (G17) Ala-Asp HB-Hradec Králové were identified. Mutations in codons 112 and 115 were described for the first time. Phenotypic manifestation of beta-thal. intermedia was revealed in three families with CD 121 (G-T) and in a family with a mutation in CD 112, but the phenotypic manifestations differed markedly in individual subjects. Heinz bodies were detected in erythrocytes of the peripheral blood in two families. An exact explanation of phenotypic deviations in patients with the same mutation even within the same family were not obtained even in studies of alpha genes and the promoter area of the beta gene. The unstable variant of Hb-Hradec Králové is manifested in the mother and daughter by haemolytic anaemia with some traits of beta-thal. The authors discuss contemporary findings from the pathophysiology of recessive and dominant beta-thal. mutations and explain some of the phenotypic consequences. A relatively high incidence of dominant beta-thal. mutations in the Czech and Slovak Republic (4 of 12 families known world wide with a nonsense beta-thal. mutation in the 3rd exon) is explained by the absence of selective preference of these mutations in malaria infested areas as a result of serious clinical manifestations in heterozygotes. The haplotype in one of the families suggests a de novo origin of the mutation in CD 121.
Subject(s)
Alleles , Codon/genetics , Genes, Dominant , Hemoglobins/genetics , Mutation , beta-Thalassemia/genetics , Adult , Aged , Child, Preschool , Czech Republic/epidemiology , Female , Humans , Male , Middle Aged , Pedigree , Slovakia/epidemiology , beta-Thalassemia/epidemiologyABSTRACT
Nuclear magnetic resonance is a method which contributes nowadays to further investigations of the phosphate metabolism in red blood cells. By means of 31P nuclear magnetic resonance it is possible to record in intact red cells signals of phosphate compounds as well as changes in their concentrations. In the submitted work the authors followed up the important phosphate compounds in red cells--adenosine triphosphate, adenosine diphosphate and inorganic phosphate. They assessed and evaluated by statistical methods spectra of 10 healthy blood donors of different age and sex. The same procedure was used in 6 patients with hereditary spherocytosis, in 6 patients with G-6-PD deficiency and in 4 patients with pyruvate kinase deficiency. The most important changes were recorded in the latter pathological entity, the results being consistent with those obtained by other methods.
Subject(s)
Anemia, Hemolytic/blood , Erythrocytes/chemistry , Magnetic Resonance Spectroscopy , Adenosine Diphosphate/blood , Adenosine Triphosphate/blood , Humans , Phosphates/bloodSubject(s)
Anemia, Hemolytic, Congenital/etiology , Glycolysis , Metabolism, Inborn Errors/complications , Pentose Phosphate Pathway , Adolescent , Adult , Anemia, Hemolytic, Congenital/epidemiology , Anemia, Hemolytic, Congenital/metabolism , Child , Child, Preschool , Czechoslovakia , Humans , Infant , Infant, NewbornSubject(s)
Adenine , Blood Preservation , Citric Acid , Glucose/analogs & derivatives , Blood Transfusion , Humans , Time FactorsABSTRACT
By means of quantitative agglutination, the results of interactions of A subgroup and variant genes with the B gene, as well as interactions of the Bx allele with A1, A2 and O genes in their heterozygous combination, are demonstrated. In the majority of interactions, competition occurs according to the rule that the allele producing the more active enzyme reduces the original activity of the enzyme produced by the relatively weaker allele. That the opposite result of interaction can occur also is shown in examples of Bx variants, when in A1Bx and A2Bx combinations complementation and a partial or nearly total normalization of the phenotypic expression of B antigen on red cells and in saliva happen. The phenomenon of competition, but even more so, the phenomenon of complementation, may have a broader importance than only for the ABO blood group system.
