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Biomedical subjects

D Labie

Publications and source records attributed to D Labie.

At least 73 records · Page 4Linked to original sources
PubMed1988

Types of alpha+ thalassemia in Southeast Asia refugees.

We have determined alpha+ deletional thalassemia among 143 Southeast Asia refugees (Cambodians, Laotians, and Vietnameses). Gene frequency of alpha+ deletional thalassemia in Vietnameses (0.035) was found lower than in Cambodians and Laotians (0.11). Bam H1 and Bg1 II analysis indicated that both rightward and leftward thalassemias are encountered, the -alpha 3,7 form is being by far more frequent than the -alpha 4.2 one. Only type I cross-over was found by Apa I digestion on -alpha 3.7 chromosomes. The Rsa I polymorphism, 5' to Z alpha 2 block, is associated with -alpha 3.7 type I haplotype and the site is present in 12 out of 23 chromosomes. All these data suggest at least three origins of alpha+-thalassemia in Cambodia and Laos.

Asia, Southeastern↗
PubMed1987

Expression of a beta thalassemia gene with abnormal splicing.

Expression of a cloned human beta thalassemia gene with a single base change at position 5 of IVS 1 has been analyzed 48 hours after transfer of the gene into HeLa cells (transient expression). Little or no normal beta globin mRNA accumulates in the presence of the abnormal beta gene in contrast to significantly more normal beta mRNA produced with other mutations at this same position. By contrast, large amounts of an abnormal beta globin mRNA are present; this is due to the use of a cryptic 5' splice site in exon 1 rather than the normal 5' splice site of IVS 1. The results indicate the variability of the effect on RNA splicing of different single base defects within IVS.

Base Sequence↗
PubMed1987

Haemoglobin disorders among Southeast-Asian refugees in France.

Haemoglobin disorders were studied among Southeast-Asian refugees (Vietnamese, Cambodians and Laotians). Phenotypic haemoglobin investigations and genotypical studies concerning the alpha loci were carried out. Most of the observed cases of microcytosis were related to a thalassaemic defect. High prevalence of Hb E and alpha-thalassaemia were found.

Asia, Southeastern↗
PubMed1987

The hematologic characteristics of sickle cell anemia bearing the Bantu haplotype: the relationship between G gamma and HbF level.

Previous work has demonstrated that the HbS gene has appeared and expanded three times in Africa in three separate geographic locations and that these three distinct mutational events can be identified by linked DNA polymorphic sites (haplotypes) surrounding the abnormal gene. We have reported that the Senegalese and Beninian haplotypes differ in G gamma expression, mean percentage of HbF, and percentage of dense cells. We now report on the third haplotype, the Bantu, and find that it has intermediate features, namely, the high mean percentage of HbF and low percentage of dense cells associated with the Senegalese haplotype, but with a low percentage of G gamma expression similar to the Beninian haplotype. The distribution of percent HbF is quite different from Senegal haplotype-bearing sickle cell anemia patients since it covers a much wider range. The low G gamma expression is also different from the Beninians since it contains a significant and unique cluster of individuals with lower than 38% G gamma. Interestingly, among the Bantu there is a strong correlation between HbF levels and G gamma expression, which is not seen with the other haplotypes. These findings open the possibility that among the Bantu haplotype-bearing individuals two chromosomal types exist that define different levels of G gamma and HbF expression. Further structural exploration of these two potential subhaplotypes is needed.

Anemia, Sickle Cell↗
PubMed1987

[Analysis of the recombination zone in hereditary persistence of fetal hemoglobin with fetal gene rearrangement of the G gamma-G gamma-A gamma type].

An increased synthesis of fetal hemoglobin in adult life is a common feature of the genetically determined severe disorders like beta thalassemia and sickle cell anemia. A continued synthesis of fetal hemoglobin in adults is also characteristic of clinical or subclinical syndromes like respectively delta beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH). These disorders are highly heterogeneous with respect to their molecular defects as well as to the composition of Hb F. We report here a novel case of hereditary persistence of fetal hemoglobin in heterozygous state discovered by chance, in a young perfectly healthy french man. The gamma chain of his fetal hemoglobin was almost entirely composed of G gamma chains. Molecular analysis of the DNA revealed the existence of triplicated gamma genes on one chromosome with the genotype arrangement of G gamma-G gamma-A gamma. A polymorphic Xmn I restriction site (at position -158 5' to the cap site) was present in 5' of both of these G gamma genes. The presence of this site in front of G gamma gene had previously been shown to be associated both with high G gamma phenotype constitutively and also with high fetal hemoglobin level only in case of anemic stress. In the absence of any anemic stress in this individual, the constitutive increase of both fetal hemoglobin and G gamma chains could be due to the presence of a chromosome with triplicated arrangement of gamma genes. The classical triplication (G gamma-A gamma-G gamma-A gamma) does not result in HPFH phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Beta thalassemia due to a novel mutation in IVS 1 sequence donor site consensus sequence creating a restriction site.

During a systematic screening of Algerian thalassemics by determining the DNA polymorphism haplotypes in the beta globin gene cluster, a novel haplotype was identified. The DNA of a homozygous individual was cloned and sequenced. The mutation, a G----A change, at position 5 of the small intervening sequence, probably interferes with normal splicing events, and, moreover, creates a new Eco RV restriction site that provides a useful diagnostic tool for detecting this condition.

Base Sequence↗
PubMed1986

Differences in DNase I sensitivity and methylation within the human beta-globin gene domain and correlation with expression.

We have analysed the chromatin features of DNA regions encompassing human epsilon, G gamma, A gamma, delta and beta globin structural genes in fetal and adult erythroid cells on the one hand and adult lymphocytes on the other. Highly purified nuclei from these cells were submitted to DNase I digestion and the kinetic data were obtained from the percentage of residual hybridization of defined regions in Southern blots. Our results, as others have shown by different approaches, indicate that the structural genes of the beta-globin cluster are generally more sensitive to DNase I in the erythroid cells than in non-erythroid cells. Thus a domain of DNase I sensitivity related to the committed state is defined. In addition we show that within this DNase-I-sensitive beta cluster domain, individual genes of the cluster are arranged in subdomains of differential DNase I sensitivity, which correlate with their expression status. Furthermore the differential expression of the two fetal genes in the fetal stage is shown to be directly proportional to the degree of hypomethylation of these genes.

Adult↗
PubMed1986

Heterogeneity of haplotypes among patients with severe Cooley disease in Eastern Sicily.

There is a large variation of clinical severity among thalassemic patients in Sicily. A heterogeneous molecular basis has already been demonstrated among the patients presenting with thalassemia intermedia. The same approach, based mostly on linked haplotypes of the beta gene cluster polymorphisms and in some cases on the demonstration of the molecular defect itself, was used to investigate 55 patients presenting with severe Cooley anemia, all maintained under permanent transfusion regimen. A large heterogeneity was demonstrated in the observed haplotypes, and only a limited overlap with those already found in thalassemia intermedia. It has been noted that many of the patients are compound heterozygotes, the various observed associations making the antenatal diagnosis at the DNA level difficult in the near future.

Adolescent↗
PubMed1986

Heterogeneity of sickle cell disease as shown by density profiles: effects of fetal hemoglobin and alpha thalassemia.

Factors that modify the intraerythrocytic concentration of hemoglobin S may influence the clinical expression of the disease. Using the phthalate ester method, the red blood cell density has been studied as a function of the mean corpuscular hemoglobin concentration. Four parameters have been used to compare the density distribution of the erythrocytes: D50 (median cell density), R60 (density range in which the middle 60% of the cells are found), F4 and F5 (proportion of cells with density greater than 1.110 and 1.120 g/ml). Compared to normal controls the density distribution of sickle red cells is heterogeneous, reproducible for the same patient (except in case of crisis), while different from one to another. The R60 is correlated with the percentage of dense cells, and the highest values for both R60 and dense cells are found when hemoglobin F is less than 10%. The highest values for the median cell density and dense red cells, but not for R60 which is normal, are observed in S/C patients. In sickle cell anemia patients, the median cell density values are not very different from the normal ones. The highest levels of hemoglobin F are found in this median subpopulation of red cells, while they are very low in the densest cells. R60 and the percentage of dense cells are not affected by the association of sickle cell disease with the deletion of one alpha gene. Their values are very near the normal ones in the case of an association with beta thalassemia or homozygous alpha thalassemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1986

Hémoglobinopathies in France.

A first approximation of the incidences of abnormal hemoglobin traits in France is given. The data include all the large ethnic minorities living in France, and also take into account the second and third generations. We estimate 1.3 X 10(5) and 1.8 X 10(5) individuals with HbS trait and beta-thalassemia trait respectively.

Anemia, Sickle Cell↗
PubMed1985

[Homozygous beta-thalassemia in Algeria. Study of 50 cases].

The clinical and laboratory data recorded at first presentation in 50 homozygous beta-thalassaemic untransfused children seen at the National Transfusion Centre, Algiers, are reported. These children came from 38 families, including 25 with consanguinous parents. Pallor was observed in all cases but jaundice and asthenia were present in only 11 and 10 children respectively. Splenomegaly was frequent (45 cases), as were skeletal changes mainly in the skull and face (35 cases). Haemoglobin levels ranged from 2.4 to 9.6 g/dl and MCV from 71 to 89 fl. Among these 50 patients, 34 had beta + thalassaemia and 16 beta 0 thalassaemia. Levels of foetal haemoglobin (Hb F) were similar in both groups but clinical symptoms appeared earlier in beta 0 thalassaemia patients. Thirty-seven cases were diagnosed as thalassaemia major and 6 as thalassaemia intermedia. Comparison of various parameters between siblings (20 children belonging to 9 families) showed no differences between Hb F and Hb A2 levels and clinical courses. These findings should be taken into consideration for the prenatal diagnosis of beta-thalassaemia.

Algeria↗
PubMed1985

Hematologically and genetically distinct forms of sickle cell anemia in Africa. The Senegal type and the Benin type.

Patients with sickle cell anemia vary in the hematologic and clinical features of their disease, in part because of variability in the presence of linked and unlinked genes that modify the expression of the disease. The hemoglobin S gene is strongly linked to three different haplotypes of polymorphic endonuclease-restriction sites of the beta-like gene cluster (genes in the vicinity of the beta-globin gene)--one prevalent in Atlantic West Africa, another in central West Africa, and yet another in Bantu-speaking Africa (equatorial, East, and southern Africa). We have studied the differences in the hematologic characteristics of patients with sickle cell anemia from the first two geographical areas. We find that the Senegalese (Atlantic West Africa) patients have higher levels of hemoglobin F, a preponderance of G gamma chains in hemoglobin F, a lower proportion of very dense red cells, and a lower percentage of irreversibly sickled cells than those from Benin (central West Africa). We interpret these data to mean that the gamma-chain composition and the hemoglobin F level are haplotype linked and that the decrease in the percentage of dense cells and irreversibly sickled cells is secondary to the elevation in the hemoglobin F level. Patients with sickle cell anemia in the New World probably correspond to various combinations of these types, in addition to the still hematologically undefined haplotype associated with sickle cell anemia in the Bantu-speaking areas of Africa.

Adult↗
PubMed1985

Membrane expansion as a mechanism explaining the antisickling action of ticlopidine observed in vitro.

Ticlopidine, a platelet antiaggregant, has shown some efficacity in a clinical trial in patients with sickle cell disease. We have studied this agent in vitro to evaluate its effects on sickle erythrocyte. Ticlopidine effects sickling in vitro not by direct interaction with hemoglobin, but via strong binding to the red cell membrane. The density of the whole cell population is decreased when cells are treated with 0.1 mM ticlopidine, which is higher than the concentrations of 1 microM potentially achievable in vivo. Since hemoglobin concentration influences the delay time for gelling, its decrease in the red cell could have a beneficial effect. Such a partial inhibition of the polymerization is shown by oxygen equilibrium studies at various ionic strengths.

Anemia, Sickle Cell↗
PubMed1985

Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients.

We have studied 42 homozygous beta-thalassemia patients from Algeria and 34 sickle cell anemia patients from Senegal and Benin, determining the relationship between haplotypes, Hb F, and G gamma-globin/A gamma-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). We find in beta-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozygotes, and the Senegal haplotype in sickle cell anemia patients are all linked to high G gamma-globin expression. In addition, haplotypes IX and Senegal, but not haplotype III, have high Hb F levels. All of these haplotype have a common subhaplotype (+- ) in the gamma-globin gene region. In addition, haplotypes IX, III, and Senegalese sickle cell anemia patients exhibit hematological amelioration of their disease. Conversely, haplotypes I, V, and A in thalassemia patients, which also have a common subhaplotype (-----), and the Benin subhaplotype (--++-) in sickle cell anemia patients are all associated with low G gamma-globin and low Hb F levels. Low G gamma-globin expression in the adult is associated with two haplotypes that are not common between thalassemia and sickle cell anemia patients. We conclude that the determinant for high G gamma-globin expression is haplotype-linked to common and genetically dominant subhaplotypes in the two diseases. The total Hb F level, unlike the high G gamma-globin expression, however, is linked to haplotypes but not to subhaplotypes, thus dissociating the two genetic effects.

Anemia, Sickle Cell↗