Heritability of fetal hemoglobin, white cell count, and other clinical traits from a sickle cell disease family cohort

Sickle cell disease (SCD) is the most common monogenic disorder in the world. Notably, there is extensive clinical heterogeneity in SCD that cannot be fully accounted for by known factors, and in particular, the extent to which the phenotypic diversity of SCD can be explained by genetic variation has not been reliably quantified. Here, in a family-based cohort of 449 patients with SCD and 755 relatives, we first show that 5 known modifiers affect 11 adverse outcomes in SCD to varying degrees. We then utilize a restricted maximum likelihood procedure to estimate the heritability of 20 hematologic traits, including fetal hemoglobin (HbF) and white blood cell count (WBC), in the clinically relevant context of inheritance from healthy carriers to SCD patients. We report novel estimations of heritability for HbF at 31.6% (±5.4%) and WBC at 41.2% (±6.8%) in our cohort. Finally, we demonstrate shared genetic bases between HbF, WBC, and other hematologic traits, but surprisingly little overlap between HbF and WBC themselves. In total, our analyses show that HbF and WBC have significant heritable components among individuals with SCD and their relatives, demonstrating the value of using family-based studies to better understand modifiers of SCD

Bilan des toxoplasmoses congénitales diagnostiquées au CHRU de Montpellier de 1985 à 2010

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Evaluation of whole-blood conservation reagents for Hematoflow-based WBC differential count: Unsatisfactory results

International audienceBackground:As conservation of whole blood samples undergoing white blood cell (WBC) differential performed by flow cytometry (Hematoflow) is needed, we evaluated the effects of two commercially available fixatives, namely TransfixTM and Streck Cell PreservativeTM.Methods:We focused on 15 normal samples and on 13 various pathological samples. We compared the two fixatives and cold- or room- temperature effects on various parameters provided by the Hematoflow system.Results:We observed that, even after 2 hours of sample treatment, the conservative methods led to significant modifications of the cell percentages due to substantial variations of the epitope expression.Conclusion:None of the different conservation methods is really reliable for WBC differential performed by flow cytometry and thus samples should be analyzed promptly or stored at 4°C

High sensitivity of the Hematoflow™ solution for chronic myelomonocytic leukemia screening

International audienceBackground: Accumulation of classical monocytes CD14++CD16– (also called MO1) ≥ 94% can accurately distinguish chronic myelomonocytic leukemia (CMML) from reactive monocytosis. The HematoFlow™ solution, able to quantify CD16 negative monocytes, could be a useful tool to manage monocytosis which remains a common issue in routine laboratories.Methods: Classical monocytes were quantified from 153 whole blood samples collected on EDTA using both flow cytometry methods, either MO1 percentage determination by the multiparameter assay previously published and regarded here as the reference method, or CD16 negative monocyte percentage determination by the means of HematoFlow™.Results: Both methods of classical monocyte percentage determination were highly and significantly correlated (r = 0.87, P < 0.0001). The HematoFlow™ solution leant toward an overestimation of the genuine classical monocyte percentages obtained by the reference method. Percentages of CD16 negative monocytes provided by HematoFlow were higher than 94% for all the 73 patients displaying classical monocytes MO1 found ≥94% by the reference method, indicating a sensitivity of 100%. Furthermore, the calculation of CD16 negative monocyte percentage can be easily computerized and integrated to the middleware.Conclusions: We propose a new application of the Hematoflow™ solution that can be used as a flag system for monocytosis management and CMML detection

Reference Values for WBC Differential by Hematoflow Analysis

International audienceObjectives - WBC differentials performed using flow cytometry with monoclonal antibodies have been developed in the last decade and are nowadays integrated into the routine workflow of some laboratories. Definition of reference values for each population is required in order to achieve an automatic validation of the results by laboratory software. Methods - We analyzed 584 samples from three hospitals using the Hematoflow solution to define the reference values. Results - Reference values are presented for five groups according to age (0-5, 6-11, 12-19, 20-69, and >69 years). Conclusions - These normal values will be helpful in the definition of relevant threshold for the automatic validation of samples analyzed by flow cytometry and the flagging of pathologic samples

Cardiovascular risk stratification in hemodialysis patients in the era of highly sensitive troponins: should we choose between hs-troponin I and hs-troponin T?

International audienceNew highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn). The present study was designed to evaluate simultaneously conventional cTnT and cTnI together with their corresponding highly sensitive determinations in stable hemodialysis (HD) patients. Ability of cTn to stratify HD patient risk was assessed

<i>TET2</i> mutational status affects myelodysplastic syndrome evolution to chronic myelomonocytic leukemia

International audienc

Multiple thrombosis in a patient with Gardos channelopathy and a new KCNN4 mutation

International audienceNo abstract availabl