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Fetal hemoglobin (Hb F) is the principal ameliorating factor of β-thalassemia (β-thal) and sickle cell disease. Persistent production in adult life is a quantitative trait regulated by loci inside or outside the β-globin gene cluster. From genome-wide association studies, principal quantitative trait loci (QTL) (accounting for 50.0% of Hb F variability in different populations) have been identified in the BCL11A gene, HBS1L-MYB intergenic polymorphism and the β-globin gene cluster itself. In this study, we analyzed quantitative trait haplotypes in two Sicilian families with extremely mild β-thal and unusually high Hb F expression, in order to examine possible genetic background variations in a similar β-thalassemic phenotype. This study redefines the linkage disequilibrium blocks at these loci, but also shows slight differences between probands in haplotype combinations which could reflect different mechanisms of high Hb F production in patients with β-thal. We proposed a haplotype-based approach as a useful tool for the understanding of β-thal phenotype variation in patients with similar β-thalassemic backgrounds in an attempt to answer the recurring question of why patients with the same β-thalassemic genotype show different phenotypes.

High HbF levels and F cells are correlated with reduced morbidity and mortality in sickle cell disease (SCD). This paper was designed to determine the HbF and F cells levels in Congolese sickle cell anemia (SCA) patients in order to determine their impact on the expression of SCD. Population and Method. HbF levels were measured in 89 SCA patients (mean age 11.4 yrs) using a standard HPLC method. F cell quantitation was done in a second group of SCA patients (n = 42, mean age 8.9 yrs) and compared with a control group (n = 47, mean age 5 yrs). F cells were quantified by a cytofluorometric system (MoAb-HbF-FITC; cut off at 0.5%). Results. The mean value of HbF was 7.2% ± 5.0 with heterogeneous distribution, most patients (76%) having HbF < 8%. Mean values of F-cells in SCA patients and control group were 5.4% ± 7.6 (median: 2.19%; range 0,0-30,3%) and 0.5% ± 1.6 (median 0.0, range 0-5.18), respectively. SCA patients with F cells >4.5% developed less painful crisis and had higher percentage of reticulocytes. Conclusion. Congolese SCA patients displayed low levels of HbF and F-cells that contribute to the severity of SCD.

Sickle cell disease is a genetic blood disorder caused by a glutamic to valine acid substitution in the beta chain of the hemoglobin protein. It was first reported in the United States where most research has been carried out on subjects of African descent. It is diffused throughout the world. Epidemiological data show that the highest incidence of sickle cell anemia is in sub-Saharan Africa where the severest forms are often fatal in children under the age of 5 years. The clinical course of the disease in Africa is comparable to that described in industrialized countries. The three cardinal symptoms are hemolytic anemia, painful episodes, and susceptibility to infection. Genotype and phenotype variations have been observed from one zone to another in Africa. Greater severity is due to a combination of various factors including constant coexistence with Plasmodium falciparum malaria and omnipresence of pyogenic factors as well as to the unfavorable demographic setting involving endogamy, poor healthcare facilities, and poor socio-economic conditions. A hundred years of research has provided a good understanding of the pathophysiological mechanisms that can sometimes be improved by to primary hydroxyurea therapy. Sickle cell disease remains a major health problem in Africa where patients do not currently benefit from the same treatment as in industrial countries.

This study concerns the molecular characterization of beta-thalassemia (beta-thal) alleles in 210 chromosomes. In the studied population, mutations were detected in 98% of the beta-thalassemic chromosomes. Twenty-one molecular defects have been found, where the five dominant mutations, IVS-I-110 (G>A), nonsense mutation at codon 39 (C>T), the frameshift codon (FSC) 6 (-A), IVS-I-1 (G>A), and IVS-I-6 (T>C), account for 80% of the independent chromosomes. Among the remaining alleles, 16 different mutations were identified, half of them being described for the first time in Algeria. These include the -101 (C>T) and the -90 (C>T) mutations in the distal and proximal promoter elements, respectively, the FSC 8 (-AA), IVS-I-5 (G>T), IVS-I-128 (T>G), FSC 47 (+A), IVS-II-1 (G>A), and the substitution in the polyadenylation signal (poly A) site AATAAA>AATGAA. Haplotype analyses on rare variants were performed. The possible origin of these mutations either by founder effect or by migrations is discussed, and raises the question of an adequate strategy to be used adapted to socio-economical status.

"A Silent Pandemic : Industrial Chemicals Are Impairing the Brain Development of Children Worldwide" Fetal and early childhood exposures to industrial chemicals in the environment can damage the developing brain and can lead to neurodevelopmental disorders (NDDs)--autism, attention deficit disorder (ADHD), and mental retardation. In a new review study, published in The Lancet, Philip Grandjean and Philip Landrigan from the Harvard School of Public Health systematically examined publicly available data on chemical toxicity in order to identify the industrial chemicals that are the most likely to damage the developing brain. The researchers found that 202 industrial chemicals have the capacity to damage the human brain, and they conclude that chemical pollution may have harmed the brains of millions of children worldwide. The authors conclude further that the toxic effects of industrial chemicals on children have generally been overlooked. In North Amercia, the commission for environmental cooperation, and in European Union the DEVNERTOX projects had reached to the same conclusions. We analyse this review and discuss these rather pessimistic conclusions.

Severe bacterial infections are the major causes of morbidity and mortality in sickle cell anemia (SCA) but are poorly explained. The distribution of a bi-allelic polymorphism (Arg107Gly) of human leukocyte antigen-E (HLA-E) locus was investigated in 144 SCA patients, most of whom originated from from sub-Saharan Africa. Among them, 73 presented with at least one severe bacterial infection, whereas 71 did not. The HLA-E*0101/E*0101 genotype was more frequent among the group with infections than their counterparts (47% vs 21%; p corrected = 0.003). This genetic association is of relevance, given the emerging evidence for the involvement of HLA-E molecules in host response to pathogens.

Phenotypic expression of sickle cell disease (SCD) is highly variable. We investigated red blood cells (RBCs) and reticulocytes using a laser light scattering method (ADVIA120, Bayer Diagnostics, Tarrytown, NY) in a series of patients with either sickle cell anemia (SS) or compound SC heterozygosity (SC), both groups with or without alpha thalassemia. Results were compared with those of a series of patients without hematological disease. Known data were consistently confirmed, namely heterogeneity in cell volume and hemoglobin (Hb) concentration, as well as the premature exit of "stress" reticulocytes from the bone marrow, mostly in SS patients. Specific changes were observed during maturation, including decreases in macrocytic and hypodense cells. Simultaneous viewing of the indices of the different RBC populations provided information on erythropoietic maturation by a rapid, reproducible, and cost-effective method.

Background and Objectives: We report on two families in which the beta(0)-thalassemia mutation IVS2+1G-->A occurs either in the homozygous or compound heterozygous condition with other beta-thalassemia determinants. In the first family the proband, homozygous for the IVS2+1 determinant, is asymptomatic and was detected by chance during a screening program for beta-thalassemia. In the second family, the proband is a 43-year old female with a very mild thalassemia intermedia due to compound heterozygosity for the IVS2+1G>A and IVS1+110G>A mutations. Her father was diagnosed as having a thalassemic disorder only during the family studies carried out because of the proband's condition. He is a compound heterozygote for the Sicilian type deltabeta(0)-thalassemia and the IVS2+1 mutation and has a normal level of hemoglobin., Design and Methods: In both families, the heterozygous carriers of the IVS2+1G>A have unusually elevated levels of fetal hemoglobin (HbF), and the homozygotes showed 98% HbF, reflecting an increased production of well hemoglobinized F-cells not associated with a significant erythroid expansion., Results: The high HbF levels co-segregate with the beta-thalassemia mutation; the size and structure of both pedigrees do not allow the contribution of unlinked genes to the elevated production of HbF to be assessed., Interpretation and Conclusions: We propose that the unusual phenotypes resulting from homozygosity and compound heterozygosity for IVS2+1 are, against the background of a polygenic quantitative control of HbF expression, principally due to elements, such as repetitive sequences or single nucleotide polymorphisms, within or closely linked to the beta-gene cluster. These are potentially implicated in chromatin environment modifications, and could, therefore, be responsible for sustained HbF synthesis during development.