@article{Fabrice Danjou_Marcella Francavilla_Franco Anni_Stefania Satta_Franca-Rosa Demartis_Lucia Perseu_Matteo Manca_Maria Carla Sollaino_Laura Manunza_Elisabetta Mereu_Giuseppe Marceddu_Serge Pissard_Philippe Joly_Isabelle Thuret_Raffaella Origa_Joseph Borg_Gian Luca Forni_Antonio Piga_Maria Eliana Lai_Catherine Badens_Paolo Moi_Renzo Galanello_2015, place={Pavia, Italy}, title={A genetic score for the prediction of beta-thalassemia severity}, volume={100}, url={https://haematologica.org/article/view/7336}, DOI={10.3324/haematol.2014.113886}, abstractNote={Clinical and hematologic characteristics of beta(β)-thalassemia are determined by several factors resulting in a wide spectrum of severity. Phenotype modulators are: <em>HBB</em> mutations, <em>HBA</em> defects and fetal hemoglobin production modulators (HBG2:g.−158C>T polymorphism, <em>HBS1L-MYB</em> intergenic region and the <em>BCL11A</em>). We characterized 54 genetic variants at these five loci robustly associated with the amelioration of beta-thalassemia phenotype, to build a predictive score of severity using a representative cohort of 890 β-thalassemic patients. Using Cox proportional hazard analysis on a training set, we assessed the effect of these loci on the age at which patient started regular transfusions, built a Thalassemia Severity Score, and validated it on a testing set. Discriminatory power of the model was high (C-index=0.705; R<sup>2</sup>=0.343) and the validation conducted on the testing set confirmed its predictive accuracy with transfusion-free survival probability (<em>P</em><0.001) and with transfusion dependency status (Area Under the Receiver Operating Characteristic Curve=0.774; <em>P</em><0.001). Finally, an automatized on-line calculation of the score was made available at <em><a href="http://tss.unica.it">http://tss.unica.it</a></em&gt;. Besides the accurate assessment of genetic predictors effect, the present results could be helpful in the management of patients, both as a predictive score for screening and a standardized scale of severity to overcome the major-intermedia dichotomy and support clinical decisions.}, number={4}, journal={Haematologica}, author={Fabrice Danjou and Marcella Francavilla and Franco Anni and Stefania Satta and Franca-Rosa Demartis and Lucia Perseu and Matteo Manca and Maria Carla Sollaino and Laura Manunza and Elisabetta Mereu and Giuseppe Marceddu and Serge Pissard and Philippe Joly and Isabelle Thuret and Raffaella Origa and Joseph Borg and Gian Luca Forni and Antonio Piga and Maria Eliana Lai and Catherine Badens and Paolo Moi and Renzo Galanello}, year={2015}, month={Mar.}, pages={452-457} }