88 results on '"Ducrocq, R."'
Search Results
2. Short insertion in a hemoglobin chain: Hb Esch, an unstable α1 variant with duplication of the sequence Ala 65-Leu-Thr-Asn 68
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Préhu, C, Groff, P, Kalmes, G, Golinska, B, Riou, J, Prome, D, Richelme-David, S, Kiger, L, Ducrocq, R, and Wajcman, H
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- 2003
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3. Purification, amplification and characterization of a population of human erythroid progenitors
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Freyssinier, J. M., Lecoq-Lafon, C., Amsellem, S., Picard, F., Ducrocq, R., Mayeux, P., Lacombe, C., and Fichelson, S.
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- 1999
4. A new alpha chain variant Hb Sallanches [alpha 2 104(G11) Cys --> Tyr] associated with HbH disease in one homozygous patient
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Morle, F., Francina, A., Ducrocq, R., Wajcman, H., Gonnet, C., Philippe, N., Souillet, G., and Godet, J.
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- 1995
5. Strategy linking several analytical methods of neonatal screening for sickle cell disease
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Ducrocq, R, Pascaud, O, Bevier, A, Finet, C, Benkerrou, M, and Elion, J
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Sickle cell anemia -- Diagnosis ,Isoelectric focusing -- Usage ,Infants -- Diseases -- Usage ,Liquid chromatography -- Usage ,Health ,Social sciences - Abstract
Abstract Background--The French national programme for the neonatal screening of sickle cell disease (SCD) was set up in 1995. This screening is targeted at newborn infants at risk. Over 5 [...]
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- 2001
6. Haemoglobinopathies: a pitfall in the assessment of glycosylated haemoglobin by ion-exchange chromatography
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Eberentz-Lhomme, C., Ducrocq, R., Intrator, S., Elion, J., Nunez, E., and Assan, R.
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- 1984
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7. Foetal haemoglobin in normal healthy adults: relationship with polymorphic sequences cis to the β globin gene.
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Zertal-Zidani, S., Ducrocq, R., Sahbatou, M., Satta, D., and Krishnamoorthy, R.
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GENETIC markers , *GENE expression , *HUMAN genetics - Abstract
We evaluated the effects of polymorphic markers within the β globin gene cluster on HbF expression in two groups. These groups were randomly selected from a survey of HbF distribution in a large population study of unrelated healthy Algerian adults (n=827). The first group contained individuals with normal HbF levels (0.1-0.5%) and the second group contained individuals with raised HbF levels (0.8-2.3%). Of the various polymorphic markers analysed, only the -309 Gγ A→G, the -158 Gγ C→T, the Gγ IVS2 TC (TG)[sub 9] AG (TG)[sub 2] (CG)[sub 2] and the -540β (AT)[sub 9] T[sub 5] sequence configurations were significantly associated with increased HbF levels. More than 84% of the subjects with elevated HbF levels carried one or several of these four marker configurations, suggesting that the β giobin gene cluster exerts a significant effect on HbF expression in healthy individuals. [ABSTRACT FROM AUTHOR]
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- 2002
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8. Two New Gγ Chain Variants: Hb F-Clamart [γ17(A14)Lys→Asn] and Hb F-Ouled Rabah [γ19(B1)Asn→Lys].
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Wajcman, H., Borensztajn, K., Riou, J., Prom, D., Hurtre, D., Bardakdjian, J., Léna-Russo, D., Amouroux, I., and Ducrocq, R.
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- 2000
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9. A novel C→A transversion within the distal CCAAT motif of the Gγ-globin gene in the algerian Gγβ+-hereditary persistence of fetal hemoglobin.
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Zertal-Zidani, S., Merghoub, T., Ducrocq, R., Gerard, N., Satta, D., and Krishnamoorthy, R.
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- 1999
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10. Compound heterozygosity Hb S/Hb Hope (β136Gly→Asp): a pitfall in the newborn screening for sickle cell disease.
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Ducrocq, R., Bévier, A., Leneveu, A., Maier-Redelsperger, M., Bardakdjian-Michau, J., Badens, C., and Elion, J.
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NEWBORN infants ,MEDICAL screening ,ISOELECTRIC focusing ,HIGH performance liquid chromatography ,GENETIC mutation - Abstract
The presence of Hb Hope associated with Hb S may represent a pitfall (false positive) in the neonatal detection of sickle cell disease by two of the most widely used analytical methods in screening programmes—isoelectric focusing (IEF) and high performance liquid chromatography (HPLC). This example illustrates the need to improve analytical strategies to avoid unnecessary anxiety and summoning of families often from a cultural background in which testing of the father is difficult to obtain. It is suggested that using two independent HPLC procedures might improve the specificity of the screening strategies. Additionally, simple procedures for detection of the most common mutations of the β globin gene on DNA extracted from dried blood specimens could be easily developed for the control of abnormal samples. These procedures could be introduced into the analytical strategy. [ABSTRACT FROM AUTHOR]
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- 1998
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11. Gamma Chain Heterogeneity: Determination of Hb F Composition by Perfusion Chromatography.
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Papassotiriou, I., Ducrocq, R., Préhu, C., Bardakdjian-Michau, J., and Wajcman, H.
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- 1998
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12. Determination of Hb F Levels: The Routine Methods.
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Préhu, C., Ducrocq, R., Godart, C., Riou, J., and Galactéros, F.
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- 1998
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13. Two Fetal Hemoglobin Variants Affecting the Same Residue: HB F-Emirates [Gγ59(E3)LYS→GLU] and HB F-Sacromonte [Gγ59(E3)LYS→GLN].
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Abbes, S., Fitzgerald, P. A., Varady, E., Girot, R., Pic, P., Blouquit, Y., Ducrocq, R., Drupt, F., and Wajcman, H.
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- 1995
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14. A new α chain variant Hb Sallanches [α2 104(G11) Cys→Tyr] associated with HbH disease in one homozygous patient.
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Morlé, F., Francina, A., Ducrocq, R., Wajcman, H., Gonnet, C., Philippe, N., Souillet, G., and Godet, J.
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- 1995
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15. Three-Year Follow-Up of Hydroxyurea Treatment in Severely Ill Children with Sickle Cell Disease.
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De Montalembert, M., Belloy, M., Bernaudin, F., Gouraud, F., Capdeville, R., Mardini, R., Philippe, N., Jais, J. P., Bardakdjian, J., Ducrocq, R., Maier-Redelsperger, M., Elion, J., Labie, D., and Girot, R.
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- 1997
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16. Molecular Basis of β-Thalassemia in Bahrain: An Epicenter for a Middle East Specific Mutationa.
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JASSIM, N., MERGHOUB, T., PASCAUD, O., AL MUKHARRAQ, H., DUCROCQ, R., LABIE, D., ELION, J., KRISHNAMOORTHY, R., and AL ARRAYED, S.
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- 1998
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17. Uremia and HbA1c measured by high-performance liquid chromatography.
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Chevenne, Didier, Fonfréde, Michele, Ducrocq, Rolande, Chauffert, Maryline, Trivin, François, Chevenne, D, Fonfrède, M, Ducrocq, R, Chauffert, M, and Trivin, F
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- 1998
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18. Short insertion in a hemoglobin chain: Hb Esch, an unstable α1 variant with duplication of the sequence Ala65-Leu-Thr-Asn68
- Author
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Préhu, C., Groff, P., Kalmes, G., Golinska, B., Riou, J., Prome, D., Richelme-David, S., Kiger, L., Ducrocq, R., and Wajcman, H.
- Subjects
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HEMOGLOBINS , *NUCLEOTIDE sequence , *DNA , *PROTEINS - Abstract
Hemoglobin (Hb) Esch, is an α1 variant, expressed at less than 5%, resulting from the duplication of the 12 nucleotides corresponding to CD65 through 68. The effect of this insertion is the repetition of the sequence Ala-Leu-Thr-Asn, which corresponds to the last turn of helix E. In this variant the presence of a one-turn elongated helix E causes instability and increased ligand affinity. Hb Esch was characterized by DNA sequencing and confirmed by electrospray mass spectrometry. Functional studies were performed by flash photolysis measurements on a fraction isolated by flatbed isoelectric focusing, which was enriched in the abnormal hemoglobin. Similar to other α chain variants due to short insertion (or deletion), Hb Esch probably results from a slipped mispairing mechanism. The stability of such modified proteins depends upon the region which is added or deleted and usually is more stable when involving a flexible loop or complete helix turn(s) near by. [Copyright &y& Elsevier]
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- 2003
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19. Perfusion Chromatography Allows an Order of Magnitude Faster Measurement of the Gγ:Aγ Ratio in Patients With an Increased Level of Fetal Hemoglobin
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Wajcman, H., Galacteros, F., and Ducrocq, R.
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- 1996
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20. Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines.
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Couque N, Girard D, Ducrocq R, Boizeau P, Haouari Z, Missud F, Holvoet L, Ithier G, Belloy M, Odièvre MH, Benemou M, Benhaim P, Retali B, Bensaid P, Monier B, Brousse V, Amira R, Orzechowski C, Lesprit E, Mangyanda L, Garrec N, Elion J, Alberti C, Baruchel A, and Benkerrou M
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- Acute Chest Syndrome etiology, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Hydroxyurea therapeutic use, Infant, Newborn, Male, Paris, Retrospective Studies, Stroke etiology, Thalassemia, Anemia, Sickle Cell complications, Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell mortality, Guideline Adherence, Quality Improvement standards
- Abstract
We conducted a retrospective study on newborns with sickle-cell disease (SCD), born 1995-2009, followed in a multicentre hospital-based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sβ°-thalassaemia) with 6776 patient-years of follow-up were analysed (mean age 7·1 ± 3·9 years). SCD-related deaths (n = 13) occurred only in SS-genotype patients at a median age of 23·1 months, mainly due to acute anaemia (n = 5, including 2 acute splenic sequestrations) and infection (n = 3). Treatment non-compliance was associated with a 10-fold higher risk of SCD-related death (P = 0·01). Therapeutic intensification was provided for all stroke patients (n = 12), almost all patients with abnormal transcranial Doppler (TCD) (n = 76) or with >1 acute chest syndrome/lifetime (n = 64) and/or ≥3 severe vaso-occlusive crises/year (n = 100). Only 2/3 of patients with baseline haemoglobin <70 g/l received intensification, mainly for other severity criteria. Overall, hydroxycarbamide was under-prescribed, given to 2/3 of severe vaso-occlusive patients and 1/3 of severely anaemic patients. Nevertheless, introduction of the on-line guidelines was concomitant with an improvement in medical care in the 2006-2009 cohort with a trend towards increased survival at 5 years, from 98·3% to 99·2%, significantly increased TCD coverage (P = 0·004) and earlier initiation of intensification of therapy (P ≤ 0·01)., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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21. Impact of glucose-6-phosphate dehydrogenase deficiency on sickle cell anaemia expression in infancy and early childhood: a prospective study.
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Benkerrou M, Alberti C, Couque N, Haouari Z, Ba A, Missud F, Boizeau P, Holvoet L, Ithier G, Elion J, Baruchel A, and Ducrocq R
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- Africa ethnology, Anemia, Sickle Cell blood, Anemia, Sickle Cell ethnology, Bilirubin blood, Blood Transfusion, Caribbean Region ethnology, Case-Control Studies, Female, Ferritins blood, Fetal Hemoglobin analysis, France, Glycogen Storage Disease Type I blood, Glycogen Storage Disease Type I ethnology, Hemoglobins analysis, Humans, Infant, Infant, Newborn, Iron blood, Male, Pain epidemiology, Pain etiology, Prospective Studies, Reticulocyte Count, Splenectomy, Stroke epidemiology, Stroke etiology, Anemia, Sickle Cell complications, Glycogen Storage Disease Type I complications
- Abstract
In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal screening, including 27 G6PD-deficient patients, who were matched on sex, age and parents' geographic origin to 81 randomly selected patients with normal G6PD activity. In the G6PD-deficient group, steady-state haemoglobin was lower (-6·2 g/l, 95% confidence interval (CI), [-10·1; -2·3]) and reticulocyte count higher (247 × 10(9) /l, 95%CI, [97; 397]). The acute anaemic event rate was 3 times higher in the G6PD-deficient group (P < 10(-3) ). A higher proportion of G6PD-deficient patients required blood transfusion (20/27 [74%] vs. 37/81 [46%], P < 10(-3) ), for acute anaemic events, and also vaso-occlusive and infectious events. No significant between-group differences were found regarding the rates of vaso-occlusive, infectious, or cerebrovascular events. G6PD deficiency in babies with SCA worsens anaemia and increases blood transfusion requirements in the first years of life. These effects decrease after 2 years of age, presumably as the decline in fetal haemoglobin levels leads to increased sickle cell haemolysis and younger red blood cells with higher G6PD activity., (© 2013 John Wiley & Sons Ltd.)
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- 2013
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22. Advantage of HbA1c assay by HPLC D-10 versus cobas integra 400 in a population carrier for HbS and HbC.
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Bouzid K, Bahlous A, Ferjani W, Kalai E, Ducrocq R, Ben Mami F, and Abdelmoula J
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- Diabetes Mellitus blood, Humans, Chromatography, High Pressure Liquid methods, Chromatography, Ion Exchange methods, Genetic Carrier Screening, Glycated Hemoglobin analysis, Hemoglobin C genetics, Hemoglobin, Sickle genetics
- Abstract
Background: Several studies demonstrate significant bias in analytical methods used to measure glycohemoglobin. The clinical importance of that fact is evident when HbA1c overestimation leads to aggressive glucose management, resulting in more frequent hypoglycaemic episodes. Our study was aimed to compare two automated instruments (Integra 400 and D-10) in the evaluation of HbA1c in the Tunisian population., Methods: Samples of 205 Tunisian diabetic patients were collected. The HbA1c assay was done simultaneously with a first generation immunoturbidimetric assay on an INTEGRA 400 (ROCHE) and using ionic exchange high pressure liquid chromatography (HPLC) on a D-10 system (BIO-RAD)., Results: Correlation is determined by linear regression analysis: D-10 = 0.921*(Integra 400) +1.125; coefficient of correlation (r) = 0.946. This r increases to 0.973 when samples of carriers for HbS and HbC (n = 9) are filtered out. For the carrier patients, significant differences in the percentage of HbA1c were observed relating to the methodology used., Conclusions: Laboratories must be aware of hemoglobin variant interferences on their methods of assessment of glycated hemoglobin. Using ion-exchange HPLC to control glycated hemoglobin seems to be essential to prevent mis-management in diabetic patients and to permit the diagnosis of the presence of HbS in patients.
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- 2012
23. Unsuspected glucose-6-phosphate dehydrogenase deficiency presenting as symptomatic methemoglobinemia with severe hemolysis after fava bean ingestion in a 6-year-old boy.
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Odièvre MH, Danékova N, Mesples B, Chemouny M, Couque N, Parez N, Ducrocq R, and Elion J
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- Algeria, Child, Eating, Favism complications, Favism physiopathology, Glucosephosphate Dehydrogenase genetics, Glucosephosphate Dehydrogenase Deficiency complications, Glucosephosphate Dehydrogenase Deficiency physiopathology, Hemolysis drug effects, Hemolytic Agents administration & dosage, Hemolytic Agents adverse effects, Humans, Male, Methemoglobinemia complications, Methemoglobinemia physiopathology, Mutation, Vicia faba adverse effects, Favism diagnosis, Glucosephosphate Dehydrogenase blood, Glucosephosphate Dehydrogenase Deficiency diagnosis, Methemoglobinemia diagnosis
- Abstract
We report the occurrence of symptomatic methemoglobinemia in a previously healthy boy, who presented with severe acute hemolysis after fava bean ingestion. The methemoglobinemia revealed a previously unrecognized glucose-6-phosphate dehydrogenase (G6PD) deficiency. We discuss the pathophysiology of severe methemoglobinemia when associated with acute hemolysis, favism, and the common African G6PD A-variant [G6PD, VAL68MET, ASN126ASP]. In conclusion, screening for G6PD deficiency must be considered in symptomatic methemoglobinemia, especially in young boys, when associated with intravascular hemolysis.
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- 2011
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24. Genetic variants in the noncoding region of RPS19 gene in Diamond-Blackfan anemia: potential implications for phenotypic heterogeneity.
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Crétien A, Proust A, Delaunay J, Rincé P, Leblanc T, Ducrocq R, Simansour M, Marie I, Tamary H, Meerpohl J, Niemeyer C, Gazda H, Sieff C, Ball S, Tchernia G, Mohandas N, and Da Costa L
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- Female, Humans, Male, Phenotype, Anemia, Diamond-Blackfan genetics, Exons genetics, Mutation, Polymorphism, Genetic, Ribosomal Proteins genetics
- Abstract
Mutations in the RPS19 gene have been identified in 25% of individuals affected by Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia characterized by an aregenerative anemia and a variety of malformations. More than 60 mutations in the five coding exons of RPS19 have been described to date. We previously reported a mutation (c.-1 + 26G>T) and an insertion at -631 upstream of ATG (c.-147_-146insGCCA) in the noncoding region. Because DBA phenotype is extremely heterogeneous from silent to severe and because haploinsufficiency seems to play a role in this process, it is likely that genetic variations in the noncoding regions affecting translation of RPS19 can modulate the phenotypic expression of DBA. However, to date, very few studies have addressed this question comprehensively. In this study, we performed detailed sequence analysis of the RPS19 gene in 239 patients with DBA and 110 of their relatives. We found that 6.2% of the patients with DBA carried allelic variations upstream of ATG: 3.3% with c.-1 + 26G>T; 2.5% with c.-147_-146insGCCA; and 0.4% with c.-174G>A. Interestingly, the c.-147_-146insGCCA, which has been found in a black American and French Caribbean control population, was not found in 500 Caucasian control chromosomes we studied. However, it was found in association with the same haplotype distribution of four intronic polymorphisms in our patients with DBA. Although a polymorphism, the frequency of this variant in the patients with DBA and its association with the same haplotype raises the possibility that this polymorphism and the other genetic variations in the noncoding region could play a role in DBA pathogenesis.
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- 2010
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25. Variants of the mannose-binding lectin gene in the Benin population: heterozygosity for the p.G57E allele may confer a selective advantage. 2007.
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Dossou-Yovo OP, Lapoumeroulie C, Hauchecorne M, Zaccaria I, Ducrocq R, Krishnamoorthy R, Rahimy MC, and Elion J
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- Adolescent, Adult, Africa epidemiology, Anemia, Sickle Cell epidemiology, Anemia, Sickle Cell history, Child, Child, Preschool, Female, Genetics, Population, HIV Infections epidemiology, HIV Infections history, History, 21st Century, Humans, Incidence, Infant, Male, Middle Aged, Mutation, Prevalence, Risk Factors, Young Adult, Anemia, Sickle Cell genetics, Genetic Variation, HIV Infections genetics, Heterozygote, Mannose-Binding Lectin genetics
- Abstract
Human mannose- binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred forty-two healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p=0.002). This enrichment was exclusively due to an elevated proportion of heterozygotes for the p.G57E allele (47.0% vs. 35.3%,respectively; p=0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV- positive patients.
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- 2009
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26. Effect of transfusion therapy on cerebral vasculopathy in children with sickle-cell anemia.
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Bader-Meunier B, Verlhac S, Elmaleh-Bergès M, Ithier G, Sellami F, Faid S, Missud F, Ducrocq R, Alberti C, Zaccaria I, Baruchel A, and Benkerrou M
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- Adolescent, Anemia, Sickle Cell diagnostic imaging, Cerebrovascular Disorders diagnostic imaging, Child, Child, Preschool, Female, Humans, Infant, Male, Radiography, Anemia, Sickle Cell complications, Anemia, Sickle Cell therapy, Blood Transfusion, Cerebrovascular Disorders complications, Cerebrovascular Disorders therapy
- Abstract
This retrospective study assessed the long-term effect of transfusional exchange therapy on MRA/MRI abnormalities in 24 homozygous sickle-cell anemia (HbSS) children presenting with abnormal brain MRA. The median time elapsed from baseline to last available MRA was 29 months. Follow-up MRAs showed improvement, stabilization or worsening of cerebrovascular lesions in 11, 6 and 7 patients respectively. Complete normalization of MRA was observed in 6 patients within a mean time of 1.4 years, but stenosis recurred at the same location in the 4 patients in whom transfusion therapy was discontinued. Baseline severe stenosis/occlusion of large cerebral arteries and occurrence of moyamoya syndrome were significantly associated with an absence of improvement of the cerebral vasculopathy. These data emphasize the heterogeneity of the course of cerebrovasculopathy in SS children receiving chronic transfusion. Further studies are needed to determine whether different therapeutic approaches have to be considered according to these different evolutive patterns in SS children.
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- 2009
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27. Neonatal screening for sickle cell disease in France.
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Bardakdjian-Michau J, Bahuau M, Hurtrel D, Godart C, Riou J, Mathis M, Goossens M, Badens C, Ducrocq R, Elion J, and Perini JM
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- Anemia, Sickle Cell epidemiology, Blood Specimen Collection methods, Chromatography, High Pressure Liquid, Electrophoresis, Agar Gel, France epidemiology, Hemoglobinopathies diagnosis, Hemoglobinopathies epidemiology, Humans, Infant, Newborn, Isoelectric Focusing, Anemia, Sickle Cell diagnosis, Neonatal Screening methods
- Abstract
Background: As a result of population growth in African-Caribbean regions of overseas France, and now immigration essentially from North and sub-Saharan Africa to mainland France, neonatal screening for sickle cell disease (SCD) has been performed in France since 1985 in Guadalupe and dependencies, as a universal test. After several pilot studies, screening was gradually extended to mainland France in 1996. Since 2000, the test has been performed at national level for all newborns defined as being "at risk" for SCD based on ethnic origin., Methods: A dry blood sample is obtained by heel stick and analysed by isoelectric focusing as a first-line method, followed by either high-performance liquid chromatography or acid agar electrophoresis for confirmation, whenever a variant haemoglobin is observed on isoelectric focusing., Results: In 2007, 28.45% of all newborns in mainland France were screened for SCD. Since 1996, a total of 3,890 newborns have been found to have SCD, and they have been followed up by reference paediatricians., Conclusion: Although screening for SCD at birth in France is not universal, it appears that missed babies are relatively infrequent. Despite obvious sociological problems inherent to the at-risk population, the follow-up of SCD babies is rather successful. Due to the birth prevalence of SCD in France, especially in comparison with other common genetic diseases, screening all newborns regardless of ethnic origin is an issue that is being addressed.
- Published
- 2009
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28. Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease.
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Odièvre MH, Bony V, Benkerrou M, Lapouméroulie C, Alberti C, Ducrocq R, Jacqz-Aigrain E, Elion J, and Cartron JP
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- Africa South of the Sahara ethnology, Anemia, Sickle Cell blood, Anemia, Sickle Cell complications, Arterial Occlusive Diseases drug therapy, Arterial Occlusive Diseases metabolism, Basigin metabolism, CD36 Antigens metabolism, CD47 Antigen metabolism, Cell Adhesion Molecules metabolism, Child, Erythrocytes chemistry, Erythroid Precursor Cells chemistry, Erythropoiesis drug effects, Follow-Up Studies, France, Gene Expression Regulation drug effects, Humans, Hydroxyurea pharmacology, Integrin alpha4beta1 metabolism, Lutheran Blood-Group System, Neoplasm Proteins metabolism, Reticulocytes chemistry, Sialic Acid Binding Ig-like Lectin 1, Signal Transduction drug effects, Anemia, Sickle Cell drug therapy, Arterial Occlusive Diseases etiology, Cell Adhesion drug effects, Cell Adhesion Molecules blood, Erythrocyte Aggregation drug effects, Hydroxyurea therapeutic use, Membrane Glycoproteins blood, Receptors, Immunologic blood
- Abstract
Background: We investigated adhesion receptor levels on red blood cells, reticulocytes and erythroid progenitors from children with sickle cell disease treated or not with hydroxyurea., Design and Methods: Four groups of patients were investigated: (i) children receiving hydroxyurea for severe vaso-occlusive events (n=26); (ii) untreated children with a history of vaso-occlusive events (n=20); (iii) children with no history of vaso-occlusive events (n=28); and (iv) healthy African controls (n=27). Expression of adhesion receptors was analyzed by flow cytometry with specific mono-clonal antibodies., Results: Reticulocytes and/or red blood cells from the children with sickle cell disease showed significantly higher expression of CD36, alpha 4beta 1, Lu/BCAM than those from controls, whatever the severity of the disease, as well as less marked increases in expression of ICAM-4, CD47 and CD147. Under hydroxyurea treatment, the expression of CD36, alpha 4beta 1 and ICAM-4 (to a lesser extent) was decreased, but surprisingly the expression of Lu/BCAM (and also CD47 and CD147 to a lesser extent) was significantly increased. Alterations of levels of adhesion receptors could be recapitulated in two-phase liquid cultures of erythroid progenitors from controls and untreated children with a history of vaso-occlusive disease, grown in the absence or presence of hydroxyurea., Conclusions: Our results suggest that hydroxyurea acts during erythroid development and modulates adhesion receptor expression and function differently, possibly by acting on gene expression and the signaling cascade leading to receptor activation.
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- 2008
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29. Molecular basis of alpha-thalassemia in Algeria.
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Mesbah-Amroun H, Rouabhi F, Ducrocq R, and Elion J
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- Algeria epidemiology, Female, Humans, Male, Molecular Epidemiology methods, alpha-Thalassemia epidemiology, Alleles, Blood Donors, Gene Frequency, Globins genetics, Mutation, alpha-Thalassemia genetics
- Abstract
An epidemiological molecular study was carried out to evaluate the spectrum and allelic frequency of alpha-thalassemia (alpha-thal) defects in Algeria. A series of 153 randomly selected blood donors was screened for 10 alpha-thal alleles described in the Mediterranean area. In addition, six unrelated cases with hematological and biochemical data suggestive of Hb H disease were investigated. Our data revealed an allele frequency of 4.6%. The presence of alpha(0)-thal determinants (-alpha(20.5) and --MED I) was observed both in Hb H patients and in the randomly collected samples. Overall, the -alpha(3.7) deletion was the most prevalent allele (2.9%), followed by the alpha(Nco I)alpha (HBA2:c.1A>G) allele (0.6%) and by the alpha(Hph I)alpha (HBA2:c.95 + 2_95 + 6delTGAGG), -alpha(20.5), --(MED I) alleles (0.3% each). The -alpha(4.2) deletion was observed in only one Hb H patient. These results outline the heterogeneity of the alpha-thal alleles in Algeria which reflects the anthropological history of the country. Because of their frequency, alpha-thal alleles are probably frequent modulators of prevalent beta-globin gene-related hemoglobinopathies in Algeria.
- Published
- 2008
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30. Variants of the mannose-binding lectin gene in the Benin population: heterozygosity for the p.G57E allele may confer a selective advantage.
- Author
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Dossou-Yovo OP, Lapoumeroulie C, Hauchecorne M, Zaccaria I, Ducrocq R, Krishnamoorthy R, Rahimy MC, and Elion J
- Subjects
- Adolescent, Adult, Alleles, Anemia, Sickle Cell epidemiology, Benin epidemiology, Humans, Infant, Newborn, Mannose-Binding Lectin deficiency, Mannose-Binding Lectin immunology, Middle Aged, Anemia, Sickle Cell genetics, Genetics, Population methods, Heterozygote, Mannose-Binding Lectin genetics
- Abstract
Human mannose-binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred forty-two healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p = 0.002). This enrichment was exclusively due to an elevated proportion of heterozygotes for the p.G57E allele (47.0% vs. 35.3%, respectively; p = 0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV-positive patients.
- Published
- 2007
- Full Text
- View/download PDF
31. The role of the G6PD AEth376G/968C allele in glucose-6-phosphate dehydrogenase deficiency in the seerer population of Senegal.
- Author
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De Araujo C, Migot-Nabias F, Guitard J, Pelleau S, Vulliamy T, and Ducrocq R
- Subjects
- Child, Female, Gene Frequency, Genotype, Glucosephosphate Dehydrogenase Deficiency ethnology, Humans, Male, Population Groups genetics, Senegal epidemiology, Senegal ethnology, Alleles, Glucosephosphate Dehydrogenase genetics, Glucosephosphate Dehydrogenase Deficiency genetics
- Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in tropical Sub-Saharan countries. The allele most frequently associated with G6PD deficiency in this a region is G6PD 376G/202A. Here, we show that, the prevalence of G6PD deficiency is 12% in the Sereer ethnic group from Senegal ant that the 376G/968C genotype is predominant; the frequency of the 376G/202A genotype is very low in this ethnic group.
- Published
- 2006
32. Decreased plasma endothelin-1 levels in children with sickle cell disease treated with hydroxyurea.
- Author
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Lapouméroulie C, Benkerrou M, Odièvre MH, Ducrocq R, Brun M, and Elion J
- Subjects
- Anemia, Sickle Cell blood, Case-Control Studies, Child, Fetal Hemoglobin analysis, Humans, Anemia, Sickle Cell drug therapy, Endothelin-1 blood, Hydroxyurea therapeutic use
- Abstract
Plasma endothelin-1 (ET-1) is elevated in patients with sickle cell disease (SCD). Hydroxyurea (HU) is the only drug with demonstrated clinical efficacy in SCD. Here we show that treatment with HU results in a decreased concentration of circulating ET-1 which is not correlated with the HU-induced increase in HbF level. Blunting of the ET-1 vasoconstrictive stimulus could contribute to the beneficial effects of HU.
- Published
- 2005
33. A new high A2-beta-thalassemia due to a 468 bp deletion (-475 to -8) in the beta-globin gene promoter of the intact beta-globin structural gene.
- Author
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Kueviakoe I, Gerard N, Krishnamoorthy R, Pereira S, Elion J, and Ducrocq R
- Subjects
- Adult, Female, Globins genetics, Humans, Promoter Regions, Genetic, Sequence Deletion, Hemoglobin A2 metabolism, beta-Thalassemia genetics, beta-Thalassemia metabolism
- Published
- 2004
- Full Text
- View/download PDF
34. Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study.
- Author
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Tubiana-Rufi N, Coutant R, Bloch J, Munz-Licha G, Delcroix C, Montaud-Raguideau N, Ducrocq R, Limal JM, and Czernichow P
- Subjects
- Blood Glucose metabolism, Body Mass Index, Child, Child, Preschool, Cross-Over Studies, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents adverse effects, Infusion Pumps, Implantable, Injections, Subcutaneous, Insulin administration & dosage, Insulin adverse effects, Insulin Lispro, Male, Parents, Postprandial Period physiology, Prospective Studies, Skin Diseases, Infectious epidemiology, Surveys and Questionnaires, Diabetes Mellitus, Type 1 drug therapy, Hypoglycemic Agents therapeutic use, Insulin analogs & derivatives, Insulin therapeutic use
- Abstract
Objective: To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII)., Study Design: 27 very young diabetic children (age 4.6 +/- 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH., Results: Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child's daily life easier (p = 0.02) and preferred LP (p = 0.01)., Conclusions: LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents' satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.
- Published
- 2004
- Full Text
- View/download PDF
35. Origin of Hb A2' (Hb B2) [delta16(A13)Gly --> Arg (GGC --> CGC)].
- Author
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Bennani M, Mombo LE, Chaventre A, Barakat A, Ducrocq R, Nagel RL, and Krishnamoorthy R
- Subjects
- Amino Acid Substitution, Base Sequence, Codon genetics, Genetic Carrier Screening, Genetic Variation, Humans, Mali, Multigene Family, Polymerase Chain Reaction methods, Arginine, Globins genetics, Glycine, Hemoglobin A2 genetics, Mutation, Missense, Polymorphism, Restriction Fragment Length
- Abstract
On a field trip to the Dogon country (le Pays Dogon) in central Mali, we detected a high frequency of the Hb A2 abnormality, reaching higher numbers among blacksmiths (up to 12.4%) living in the same villages. In this report, by direct nucleotide sequencing and employing a polymerase chain reaction-restriction fragment length polymorphism approach, we show that the Hb A2 variant observed in the Dogon population is indeed Hb A2', also called Hb B2, and that in all of the cases the abnormal delta-globin gene is linked to a unique haplotype. The same haplotype was found linked to Hb A2' in the Herero population belonging to the South African Bantu-speaking Blacks from Namibia. Although the unique origin of this mutation in Africa is a possibility, a recurrent mutational event cannot be excluded because the linked beta cluster haplotype is one of the two major haplotypes found in all African populations. A study of populations from other regions of Africa is required to clarify this issue.
- Published
- 2003
- Full Text
- View/download PDF
36. A novel rearrangement of the human fetal globin genes leading to a six gamma-globin gene haplotype.
- Author
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Gonçalves I, Lavinha J, Ducrocq R, and Osório-Almeida L
- Subjects
- Adult, Chromosome Mapping, Female, Haplotypes, Humans, Male, Portugal, Fetal Proteins genetics, Gene Rearrangement, Globins genetics, Hypergammaglobulinemia genetics
- Abstract
Haematological as well as gene mapping data are reported for three members of a Portuguese Caucasian family with high G(gamma)-globin levels. A gamma-globin gene sextuplication of the G(gamma)AG(gamma)AG(gamma)AG(gamma)AG(gamma)A(gamma) type was present in the proband and her father. Comparison of gene mapping data with quantitative results of fetal haemoglobin (HbF) analysis provided an explanation for the extremely high G(gamma)-globin levels (> 90%) in the HbF from the two mentioned individuals. This rearrangement, for which a generation mechanism is proposed, is the first gamma-globin gene sextuplication described in the literature.
- Published
- 2002
37. A novel delta beta fusion gene expresses hemoglobin A (HbA) not Hb Lepore: Senegalese delta(0)beta(+) thalassemia.
- Author
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Zertal-Zidani S, Ducrocq R, Weil-Olivier C, Elion J, and Krishnamoorthy R
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Family Health, Female, Globins genetics, Humans, Male, Middle Aged, Nuclear Family, Pedigree, Promoter Regions, Genetic genetics, Senegal, beta-Thalassemia genetics, Hemoglobin A genetics, Hemoglobins, Abnormal genetics, Sequence Deletion genetics
- Abstract
This study identified and characterized a novel delta beta fusion gene in which the delta-globin gene promoter is linked to intact beta-globin coding sequences in a Senegalese family. It results from a 7.4-kb deletion that removes the delta-globin coding sequences, the delta beta intergenic region as well as the beta-globin gene promoter and causes delta(0)beta(+) thalassemia with hemoglobin A expressed at the 11% to 15% range. The phenotype of this naturally occurring delta beta hybrid gene not only clarifies, in an in vivo context, the respective strength of delta- and beta-globin gene promoters, but also emphasizes the importance of beta-globin intragenic sequences in the expression of beta-globin chains. (Blood. 2001;98:1261-1263)
- Published
- 2001
- Full Text
- View/download PDF
38. Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease.
- Author
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Neonato MG, Guilloud-Bataille M, Beauvais P, Bégué P, Belloy M, Benkerrou M, Ducrocq R, Maier-Redelsperger M, de Montalembert M, Quinet B, Elion J, Feingold J, and Girot R
- Subjects
- Acute Disease, Adolescent, Anemia, Sickle Cell genetics, Child, Child, Preschool, Cohort Studies, Female, France epidemiology, Genotype, Humans, Male, Meningitis complications, Meningitis epidemiology, Osteomyelitis complications, Osteomyelitis epidemiology, Phenotype, Risk Factors, Sepsis complications, Sepsis epidemiology, Stroke complications, Stroke epidemiology, alpha-Thalassemia complications, alpha-Thalassemia genetics, Anemia, Sickle Cell complications
- Abstract
A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.
- Published
- 2000
- Full Text
- View/download PDF
39. Two new Ggamma chain variants: Hb F-clamart [gamma17(A14)Lys-->Asn] and Hb F-Ouled Rabah [gamma19(B1)Asn-->Lys].
- Author
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Wajcman H, Borensztajn K, Riou J, Promé D, Hurtrel D, Bardakdjian J, Léna-Russo D, Amouroux I, and Ducrocq R
- Subjects
- Africa, Northern ethnology, Algeria ethnology, Amino Acid Substitution, Chromatography, High Pressure Liquid, Family Health, France epidemiology, France ethnology, Genetic Variation, Heterozygote, Humans, Infant, Newborn, Molecular Weight, Morocco ethnology, Neonatal Screening, Tunisia ethnology, alpha-Thalassemia genetics, Fetal Hemoglobin chemistry, Fetal Hemoglobin genetics, Globins chemistry, Globins genetics, Hemoglobins, Abnormal chemistry, Hemoglobins, Abnormal genetics
- Abstract
Two new fetal hemoglobin variants affecting the Ggamma chain are reported. Hb F-Clamart was found during investigation of a French newborn who presented with a mild microcytemia. The second variant was found during neonatal screening for hemoglobinopathies of 30,000 babies from a population-at-risk living in the Paris region. It was named Hb F-Ouled Rabah because its structural modification and ethnic distribution is similar to that of Hb D-Ouled Rabah [beta19(B1)Asn-->Lys]. Hb F-Ouled Rabah is clinically silent and occurs at a frequency of ca. 0.1% in newborns originating from Maghreb. Structural characterization of both variants was done by protein chemistry methods, including amino acids analysis and mass spectrometry.
- Published
- 2000
- Full Text
- View/download PDF
40. Spectrum of beta thalassemia mutations and their linkage to beta-globin gene haplotypes in the Indo-Mauritians.
- Author
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Kotea N, Ramasawmy R, Lu CY, Fa NS, Gerard N, Beesoon S, Ducrocq R, Surrun SK, Nagel RL, and Krishnamoorthy R
- Subjects
- Alleles, Humans, Mauritius, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Genetic Linkage, Globins genetics, Haplotypes, Mutation, beta-Thalassemia genetics
- Abstract
The beta thalassemia alleles in 53 thalassemic Indo-Mauritian patients and their families consisting of 23 homozygous beta-thalassemia, 9 HbE/beta-thalassemia, 18 HbS/beta-thalassemia, 1 HbD/beta-thalassemia, 1 deltabeta/beta-thalassemia and 1 HbH/beta-thalassemia from the island of Mauritius were studied. Characterization by polymerase chain reaction-based reverse dot blot hybridization technique revealed that the IVS1-5 (G-->C) mutation accounted for 74% of the beta thalassemic alleles, while six other mutations occurred at much lower frequencies: HbE codon 26 (G-->A); 10.4%, codon 8/9 (+G); 3.5%, codon 30 (AGG-->ACG) also called IVSI (-1).G-->C; 3.5%, codon 15 (G-->A); 3.5%, codon 41/42 (-CTTT); 2.4% and -28 (A-->G); 2.4%. Association of these mutations to specific beta globin gene sequence framework and haplotype allowed to trace their ancestral link. These data are useful in future molecular screening of the population in view of implementing a thalassemia prevention and control program in Mauritius., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
- Full Text
- View/download PDF
41. Evaluation of the Tosoh HLC-723GHb V A1c 2.2 hemoglobin A1c analyzer.
- Author
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Chevenne D, Marle N, Chauffert M, Noel M, Ducrocq R, and Trivin F
- Subjects
- Automation, Chromatography, High Pressure Liquid methods, Diabetes Mellitus metabolism, Erythrocytes metabolism, Evaluation Studies as Topic, Hemoglobin C analysis, Humans, Regression Analysis, Reproducibility of Results, Chromatography, High Pressure Liquid instrumentation, Glycated Hemoglobin analysis
- Published
- 1999
- Full Text
- View/download PDF
42. A novel C-->A transversion within the distal CCAAT motif of the Ggamma-globin gene in the Algerian Ggammabeta+-hereditary persistence of fetal hemoglobin.
- Author
-
Zertal-Zidani S, Merghoub T, Ducrocq R, Gerard N, Satta D, and Krishnamoorthy R
- Subjects
- Adolescent, Adult, Aged, Algeria, Child, Female, Fetal Hemoglobin metabolism, Haplotypes, Humans, Male, Middle Aged, Multigene Family, Pedigree, Fetal Hemoglobin genetics, Globins genetics, Point Mutation
- Abstract
Hereditary persistence of fetal hemoglobin (HPFH) is a group of genetically heterogeneous conditions characterized by the continued expression of fetal hemoglobin in adulthood. These constitute natural models for understanding the mechanism(s) of the hemoglobin switch. Many large deletions in the beta-globin gene cluster and point mutations in one of the fetal globin gene promoters have been described before. In this study we describe a novel C-->A transversion (-114) in the distal CCAAT box of the Ggamma-globin gene promoter associated with the Ggammabeta+-HPFH phenotype in an Algerian family. Individuals heterozygous for this mutation exhibit moderate raise in Hb F levels (0.6-3.5%). Much higher Hb F levels (3.8-11.2%) are observed when a beta(o)-thalassemia allele is present in trans to the hereditary persistence of fetal hemoglobin allele. This novel Algerian HPFH mutation further stresses the importance of the distal CCAAT box in the postnatal regulation of gamma-globin gene expression.
- Published
- 1999
- Full Text
- View/download PDF
43. New method for quantitative determination of fetal hemoglobin-containing red blood cells by flow cytometry: application to sickle-cell disease.
- Author
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Navenot JM, Merghoub T, Ducrocq R, Muller JY, Krishnamoorthy R, and Blanchard D
- Subjects
- Adult, Erythrocytes immunology, Fetal Blood cytology, Hemoglobin SC Disease blood, Humans, Erythrocytes chemistry, Fetal Hemoglobin analysis, Flow Cytometry methods
- Abstract
A new method to quantify red blood cells (RBCs) containing fetal hemoglobin (HbF), or F cells, by flow cytometry was developed. The use of formaldehyde as fixative agent and sodium dodecyl sulfate (SDS) to permeabilize fixed RBCs resulted in a low staining background, a negligible Hb leakage, and minimal cell clumping. HbF was detected by immunofluorescence with a murine monoclonal antibody directed to the gamma chain of human Hb. The accuracy of the F-cell count was evaluated on mixed-field populations of adult and cord RBCs. The results of flow cytometry were highly correlated with HbF dosage in the hemolysate by high-pressure liquid chromatography (HPLC) (R > 0.99). The sensitivity of the method allowed the study of HbF distribution at the single-cell level in normal controls and patients with sickle-cell disease (SCD). All patients exhibited a heterocellular distribution of HbF, with highly variable percentages of F cells and non-F cells. As an additional and valuable biological parameter in SCD, the mean HbF content per F cell could be deduced from the measurement of HbF level by HPLC and F-cell count by flow cytometry. Results were unchanged after storing the cells for several weeks in an optimized resuspending solution. Since it does not need uncommon reagents or devices and allows the simultaneous detection of membrane antigens by two-color flow cytometry, this method is convenient for routine laboratories as well as for research purposes.
- Published
- 1998
44. Molecular basis of beta-thalassemia in Bahrain: an epicenter for a Middle East specific mutation.
- Author
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Jassim N, Merghoub T, Pascaud O, al Mukharraq H, Ducrocq R, Labie D, Elion J, Krishnamoorthy R, and Arrayed SA
- Subjects
- Alleles, Bahrain, Chromosome Mapping, Hemoglobins genetics, Humans, Middle East, Point Mutation, Sequence Deletion, Mutation, beta-Thalassemia genetics
- Published
- 1998
- Full Text
- View/download PDF
45. Fetal hemoglobin and F-cell responses to long-term hydroxyurea treatment in young sickle cell patients. The French Study Group on Sickle Cell Disease.
- Author
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Maier-Redelsperger M, de Montalembert M, Flahault A, Neonato MG, Ducrocq R, Masson MP, Girot R, and Elion J
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Male, Time Factors, Anemia, Sickle Cell blood, Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell pathology, Antisickling Agents administration & dosage, Fetal Hemoglobin metabolism, Hydroxyurea administration & dosage, Reticulocytes metabolism
- Abstract
We have studied the cellular and molecular responses to long-term hydroxyurea (HU) treatment in 29 severely affected young patients with sickle cell disease (mean age, 10.9 +/- 4.1 years). Patients received HU at 20 mg/kg/d on 4 consecutive days per week initially, with a monthly escalated dose avoiding marrow-toxicity (mean steady-state dose, 34.2 +/- 4.6 mg/kg/d) for 12 to 36 months (mean duration, 22 months). The studied parameters were hemoglobin F (HbF), F reticulocytes (F retics), F cells, the amount of HbF per F cell (F/F cell), polymer tendency at 40% and 70% oxygen saturation, and hemolysis. Initial HbF (Fi) was dispersed (from 0.85% to 13.9%). HbF increased in all patients but 1. HbF at maximal response (Fmax) reached a sustained level varying from a 1.5-fold to a 16-fold Fi after a variable delay (6 to 24 months). Fmax was not related to HU dosage, but triangle upF (Fmax - Fi) was strongly correlated to triangle upMCV (MCVmax - MCVi). HbF increase resulted from the increase of both F cells and F/F cell. In this rather short series, Fi and Fmax were not significantly associated with age, gender, or beta-globin haplotype. Neither Fmax nor triangle upF was related to bone marrow reserve, as measured by baseline reticulocyte or neutrophil counts. However, Fmax was highly dependent on Fi. When patients are individualized into three groups according to Fmax (group 1, Fmax >20% [12 patients]; group 2, 10% < Fmax < 20% [11 patients]; group 3, Fmax <10% [5 patients]), Fi is significantly different between groups, being the highest in group 1. In addition, the best responders (group 1) were significantly different from patients in the two other groups with higher levels of total hemoglobin, decreased bilirubin, and decreased polymer tendency.
- Published
- 1998
46. Combined effect of two different polymorphic sequences within the beta globin gene cluster on the level of HbF.
- Author
-
Gonçalves I, Ducrocq R, Lavinha J, Nogueira PJ, Peres MJ, Picanço I, Correia E Jr, Reis AB, Silva C, Krishnamoorthy R, and Almeida LO
- Subjects
- Adolescent, Adult, Aged, Alleles, Child, Preschool, Female, Gene Expression Regulation, Haplotypes, Hemoglobins, Abnormal genetics, Humans, Male, Pedigree, Polymorphism, Restriction Fragment Length, beta-Thalassemia genetics, Fetal Hemoglobin genetics, Globins genetics, Hemoglobinopathies genetics
- Abstract
Beta thalassemia and Hb Lepore heterozygotes included in this study exhibit fetal hemoglobin levels varying from trace quantities to 14% (1.74 g/dl) of total hemoglobin in the adult. In this work, we have examined the correlation of DNA sequence polymorphisms with the observed HbF level. The analysis of polymorphic markers within the beta globin cluster in 39 individuals heterozygous for beta thalassemia or Hb Lepore confirms the previous findings for homozygous beta thalassemia: the presence of both an (AT)9 T5 sequence configuration at position -540 of the beta globin gene and a (C --> T) variation at -158 of the Ggamma globin gene is associated with elevated expression of HbF. However, at least one defective beta globin gene is required to reveal this association. The best evidence is from the study of individuals heterozygous for Hb Lepore with various levels of HbF. In these individuals it was possible to explore the effect of a single (AT)x Ty motif (the other being absent from the rearranged Lepore chromosome) on HbF expression. The presence of the (AT)9 T5 configuration increases HbF level from a median of 0.515 g/dl observed in (AT)7 T7 subjects, to 1.39 g/dl. We confirm the existence of linkage disequilibrium between the (C --> T) variation at -158 of Ggamma gene and the (TG)13 configuration at the second intervening sequence (IVS-2) of Agamma gene and identify two new polymorphisms in this region: (TG)7 (CG)5 (TG)8 linked to haplotype V and (TG)8 (CG)5 (TG)10 linked to haplotype II. This study suggests that two distinct regions of the beta cluster, whether in cis or in trans to each other, can interact to enhance HbF expression when a beta thalassemic determinant is present in heterozigosity.
- Published
- 1998
- Full Text
- View/download PDF
47. Compound heterozygosity Hb S/Hb Hope (beta 136 Gly-->Asp): a pitfall in the newborn screening for sickle cell disease.
- Author
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Ducrocq R, Bévier A, Leneveu A, Maier-Redelsperger M, Bardakdjian-Michau J, Badens C, and Elion J
- Subjects
- Anemia, Sickle Cell genetics, Aspartic Acid genetics, Chromatography, High Pressure Liquid, Glycine genetics, Humans, Infant, Newborn, Isoelectric Focusing, Point Mutation, Anemia, Sickle Cell diagnosis, Genetic Carrier Screening, Hemoglobin, Sickle genetics, Hemoglobins, Abnormal genetics, Neonatal Screening
- Abstract
The presence of Hb Hope associated with Hb S may represent a pitfall (false positive) in the neonatal detection of sickle cell disease by two of the most widely used analytical methods in screening programmes-isoelectric focusing (IEF) and high performance liquid chromatography (HPLC). This example illustrates the need to improve analytical strategies to avoid unnecessary anxiety and summoning of families often from a cultural background in which testing of the father is difficult to obtain. It is suggested that using two independent HPLC procedures might improve the specificity of the screening strategies. Additionally, simple procedures for detection of the most common mutations of the beta globin gene of DNA extracted from dried blood specimens could be easily developed for the control of abnormal samples. These procedures could be introduced into the analytical strategy.
- Published
- 1998
- Full Text
- View/download PDF
48. Dissection of the association status of two polymorphisms in the beta-globin gene cluster with variations in F-cell number in non-anemic individuals.
- Author
-
Merghoub T, Perichon B, Maier-Redelsperger M, Dibenedetto SP, Samperi P, Ducrocq R, Feingold N, Elion J, Schiliro G, Labie D, and Krishnamoorthy R
- Subjects
- Adult, Aged, Anemia, Sickle Cell metabolism, Anemia, Sickle Cell pathology, DNA analysis, Erythrocyte Count, Female, Fetal Hemoglobin biosynthesis, Gene Expression Regulation, Genetic Markers, Haplotypes genetics, Humans, Male, Middle Aged, Polymerase Chain Reaction, Site-Specific DNA-Methyltransferase (Adenine-Specific) genetics, Anemia, Sickle Cell genetics, Fetal Hemoglobin genetics, Globins genetics, Multigene Family, Polymorphism, Genetic
- Abstract
Expression of fetal hemoglobin (Hb F) is under polygenic control involving determinants both linked and unlinked to the beta-globin gene cluster on chromosome 11. Variations in the DNase I-hypersensitive site 2 of the locus control region (LCR-HS2) and a C --> T change at position -158 from the Ggamma-gene (detected as an XmnI polymorphism) correlate with the high level of Hb F expression in patients with sickle-cell anemia and beta-thalassemia. Interpretation of data under these conditions of anemic stress is difficult because the preferential survival of Hb F-containing erythrocytes (F-cells) may not reflect the true status of Hb F expression. We investigated the relationship between these markers and Hb F expression in terms of F-cell levels in 48 unrelated non-anemic AS heterozygotes from Sicily. The betaS-chromosome of all these individuals was of the Benin haplotype and they differed only by their betaA chromosomes. We demonstrate that F-cell expression is more strongly associated with LCR-HS2 polymorphism than with XmnI polymorphism. The observed association between XmnI polymorphism and Hb F expression is very likely to be due to linkage disequilibrium with LCR-HS2 sequences.
- Published
- 1997
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- View/download PDF
49. Polymorphism in exon 10 of the human coagulation factor V gene in a population at risk for sickle cell disease.
- Author
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Helley D, Besmond C, Ducrocq R, da Silva F, Guillin MC, Bezeaud A, and Elion J
- Subjects
- Africa South of the Sahara, Africa, Northern, Anemia, Sickle Cell complications, Europe, Exons, Humans, Risk, Thrombosis complications, West Indies, Anemia, Sickle Cell genetics, Factor V genetics, Polymorphism, Genetic, Thrombosis genetics
- Abstract
In Caucasians, the R506Q mutation in exon 10 of the factor V gene (FV Leiden) confers an increased risk of thromboembolism. We have scanned this region of the gene for possible mutations in 450 subjects from populations at risk for sickle cell disease (SCD). The R506Q mutation was absent in subjects from sub-Saharan Africa, whereas its allelic frequency was 2.5% in the West Indies. Only one other substitution with no functional consequences in vitro (R485K) was found (32.4% allelic frequency) in sub-Saharan Africa. Thus, we found no mutations in exon 10 of the FV gene constituting an additional risk factor for thrombosis in SCD in sub-Saharan Africa. This suggests that the putative selective advantage conferred by R506Q does not exist in these populations, unless R485K has functional consequences in vivo. If further suggests that R506Q in American Africans is of Caucasian origin. Our data are the first to document ethnic variations in the frequency of the R485K polymorphism.
- Published
- 1997
- Full Text
- View/download PDF
50. Effect of alpha-thalassemia on sickle-cell anemia linked to the Arab-Indian haplotype in India.
- Author
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Mukherjee MB, Lu CY, Ducrocq R, Gangakhedkar RR, Colah RB, Kadam MD, Mohanty D, Nagel RL, and Krishnamoorthy R
- Subjects
- Fetal Hemoglobin genetics, Gene Expression, Globins genetics, Haplotypes, Hemoglobin, Sickle genetics, Heterozygote, Humans, India, Restriction Mapping, Anemia, Sickle Cell genetics, alpha-Thalassemia genetics
- Abstract
Two population groups from Western India with a high prevalence of the beta(S) gene, one tribal (Valsad) and the other nontribal (Nagpur), were studied. The beta(S) gene frequency in both populations was similar (0.22 vs. 0.23), but not the clinical expression of sickle-cell anemia (SS): the sickle homozygotes in the tribal group appeared to have a mild clinical course, whereas the majority in the nontribal group exhibited a more severe clinical phenotype. Both tribal and nontribal SS patients had a similarly high mean hemoglobin (Hb)F expression (18.5% vs. 15.5%) and a high number of F cells (72.3% vs. 66.6%). DNA analysis of the beta-globin gene cluster region revealed that in these two populations, this portion of DNA was identical with and corresponded to the typical Arab-Indian haplotype. Nevertheless, in heterozygotes, the mean beta(S) expression was lower (27.9%) in the tribal as compared to the nontribal group (35.5%). The major epistatic factor distinguishing the milder presentation in tribals vs. a more severe manifestation in nontribals was the very high frequency (0.97) of the alpha-thalassemia gene in the former as compared to the latter (0.24). We conclude that the phenotypic expression of sickle-cell anemia, linked to the Arab-India haplotype and expressing similar levels of HbF and F cells, is not uniformly mild in India and that alpha-thalassemia is a powerful and additional epistatic factor in the Indian subcontinent.
- Published
- 1997
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