Diverse genetic mechanisms operate to generate atypical betaS haplotypes in the population of Guadeloupe.

In a survey of the chromosomal background associated with the sickle cell gene in Guadeloupe, a French Caribbean island, we identified 37 unrelated patients with sickle cell disease (27 SS, nine SC, and one S-beta-thalassemia) of 477 unrelated sickle cell patients where the beta3 gene was linked to 20 different atypical haplotypes. These atypical chromosomes account for about 5% of the overall betaS chromosomes in this population. To investigate the origin of these atypical betaS haplotypes, we performed extensive typing of betaS and betaA chromosomes.

Prevalence, clinical features, and risk factors of osteonecrosis of the femoral head among adults with sickle cell disease.

This prospective study examined the prevalence, clinical features, and risk factors of osteonecrosis of the femoral head among adult sickle cell disease patients in Guadeloupe. Screening of osteonecrosis of the femoral head was performed using radiography, bone scintigraphy, and tomodensitometry. One hundred thirteen adults with sickle cell disease (67 SS and 46 SC patients) comprised the study population.

Morphological features of the human umbilical vein in normal, sickle cell trait, and sickle cell disease pregnancies.

Pathological changes often occur in the placenta of women with sickle cell disease (SCD). These alterations are caused by sickling of erythrocytes and vasoocclusion in the placental circulation, leading to regional hypoxia. However, the morphological status of the umbilical cord, which is in close physical association with the placenta, is not documented under such conditions.

Genetic and hematological studies in a group of 114 adult patients with SC sickle cell disease.

The clinical and biological heterogeneity of sickle cell hemoglobin (Hb) C disease (SC disease) is similar to sickle cell anemia, but has a much milder course. The effect of genetic factors such as alpha thalassemia or beta-globin gene haplotype has been analyzed in a limited number of cases. In this work, we report about 114 adult SC patients, aged 15 to 65 years (M/F = 0.

Prevalence of fragile-X syndrome and FRAXE among children with intellectual disability in a Caribbean island, Guadeloupe, French West Indies.

Fragile-X syndrome (FXS) is the most common cause of inherited intellectual disability. Although FXS has been identified in all the main ethnic groups, little is known about its prevalence with respect to ethnicity. Since the identification of the FXS primary defect, diagnosis involving DNA analysis has been made possible, allowing efficient screening strategies to be considered.

Sickle cell disorder, beta-globin gene cluster haplotypes and alpha-thalassemia in neonates and adults from Guadeloupe.

We have studied haplotype of beta(S) chromosome and alpha-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-beta-thal (n = 56), and other rare forms (n = 10). Haplotype data on beta(S) chromosomes confirm our previous observation that Benin type is the most prevalent (75%) beta(S) chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various beta(S) haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current beta(S) haplotype distribution in this island is not distorted by haplotype-related differential survival.

[Conditions of use and access to care of sickle cell anemia patients. Analysis of the literature].

In order to identify the care access and life conditions and non-compliance risk factors of sickle-cell patients, we performed a literature survey on these subjects, and on other chronic pathologies and care systems used as references. The data showed a positive influence of good quality of life, social support and family environment on diabetes mellitus patients compliance, and the negative effect of poor socioeconomic status on adequate prenatal care. Concerning sickle-cell disease, there were few data on the non-compliance risk factors.

Efficiency of prenatal counselling for sickle cell disease in Guadeloupe.

As in most caribbean countries, Sickle Cell Disease (SCD) is a major public health problem in Guadeloupe. A prenatal counselling program was developed, at an early stage of pregnancy, for at-risk couples. Over a 6 year period, 144 couples at-risk of having a child with homozygous sickle cell (SS: n = 103) or sickle cell C disease (SC: n = 41) were seen for prenatal counselling.

Molecular characterization of beta-thalassemia mutations in Guadeloupe.

In order to perform genetic counselling and prenatal diagnosis of Hb-S-beta-thalassemia disease and beta-thalassemia, we have delineated the spectrum of beta-thalassemia alleles in the Guadeloupean population. A sample of 63 unrelated families was analyzed including 70 beta-thalassemia carriers, 52 Hb-S-beta-thalassemia, and 8 patients with different beta-thalassemic hemoglobinopathies. Among the eleven mutations identified, four of them [-29 (A --> G), IVS-I-5 (G --> A), IVS-II-1 (G --> A), and IVS-I-5 (G --> C)] account for 77.

beta S haplotypes, alpha-globin gene status, and hematological data of sickle cell disease patients in Guadeloupe (F.W.I.).

The beta gene cluster haplotypes, alpha gene status, Hb F level and hematological parameters have been characterized in 154 unrelated Guadeloupe patients with sickle cell disease: 112 with sickle cell anemia, 26 with SC disease, 15 with Hb S-beta-thalassemia, and one patient with Hb S in association with the hereditary persistence of fetal hemoglobin. Fourteen haplotypes in 16 combinations were found, the three major African haplotypes were present on 92% of all chromosomes: 73% Benin, 11% Bantu, 8% Senegal. Among SS patients, 57% were Benin homozygotes, one patient was a Senegal homozygote, one patient was a Bantu homozygote, and all the others were heterozygous.

Characterization of phosphoinositide kinases in normal and sickle anaemia red cells.

PtdIns and PtdInsP kinases from normal erythrocyte (AA) membranes and sickle cell anaemia erythrocyte (SS) membranes have been characterized. PtdIns kinase was studied in native membranes under conditions in which PtdInsP kinase and PtdInsP phosphatase do not express any activity. Kinetic analysis of the AA and SS PtdIns kinases indicate similar Km values for PtdIns and ATP but higher Vmax values for SS PtdIns kinase.

[Health policies and sickle cell disease].

Issues of public health raised by sickle cell disease and available solutions vary greatly between countries. Two main variables lead the choices: the affordable health resources, and the distribution of the abnormal genes in the population. Three examples have been chosen to illustrate these challenges.

Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes.

We have found a sickling variant, Hb S Antilles, alpha 2 beta 2(6 Glu----Val, 23 Val----Ile), that has the same electrophoretic mobility as Hb S but a distinct isoelectric focus and produces sickling in the carriers of the Hb A/S Antilles trait. The carriers' erythrocytes tend to sickle at O2 partial pressures similar to those that induce sickling in Hb S/C disease. Pure deoxy-Hb S Antilles is 50% as soluble as deoxy-Hb S (saturating concentration = 11 g X dl-1 compared to 18.

Hemoglobin La Desirade alpha A2 beta 2 129 (H7) Ala----Val: a new unstable hemoglobin.

Hemoglobin La Desirade is a new unstable hemoglobin variant arising from the substitution of beta 129 (H7) Ala for Val. Hb La Desirade exhibits a low oxygen affinity and normal heme-heme interaction. The variant was found in two unrelated black families in association with Hb S, Hb C or beta o thalassemia.

Hemoglobin Roseau-Pointe a Pitre alpha 2 beta 2(90) (F6) Glu----Gly: a new hemoglobin variant with slight instability and low oxygen affinity.

A Dominican neonate carrying a new abnormal hemoglobin, hemoglobin Roseau Pointe-à-Pitre alpha 2 beta 2(90)(F6) Glu----Gly, was detected in Guadeloupe during application of a cord blood screening program. This variant behaved in isoelectrofocusing as an Hb D, and displayed instability and low whole blood oxygen affinity. In the affected family it was present, either isolated, or in association with a beta+ thalassemia trait.

Kinetic anticooperativity in pre-steady-state formation of tryptophanyl adenylate by tryptophanyl-tRNA synthetase from beef pancreas. A consequence of the tryptophan anticooperative binding.

The kinetics of formation of tryptophanyl adenylate by tryptophanyl-tRNA synthetase from beef pancreas has been followed by stopped-flow, using the quenching of fluorescence of the enzyme linked to the amino acid activation reaction. Both subunits of this alpha 2 enzyme catalyze the adenylate formation. At saturation with substrates the rate constant of the activation reaction is the same for both subunits.

Aminoacylation of tRNA Trp from beef liver, yeast and E. coli by beef pancrease tryptophan-tRNA ligase. Stoichiometry of tRNATrp binding.

The Michaelis constants and the maximum velocities in the aminoacylation reaction of tRNATrp from beef liver, yeast and E. coli by pure beef pancreas tryptophan-tRNA ligase show that this mammalian enzyme recognizes and charges the two eucaryotic tRNAs with the same efficiency. The rate of aminoacylation of the procaryotic tRNATrp by the enzyme is three orders of magnitude lower.