caa a22 4500 445807865 CHVBK 20180317145202.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00415-011-5979-z doi (NATIONALLICENCE)springer-10.1007/s00415-011-5979-z Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up [Elektronische Daten] [Francesca Magri, Alessandra Govoni, Maria D'Angelo, Roberto Del Bo, Serena Ghezzi, Gandossini Sandra, Anna Turconi, Monica Sciacco, Patrizia Ciscato, Andreina Bordoni, Silvana Tedeschi, Francesco Fortunato, Valeria Lucchini, Sara Bonato, Costanza Lamperti, Domenico Coviello, Yvan Torrente, Stefania Corti, Maurizio Moggio, Nereo Bresolin, Giacomo Comi] Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) are allelic disorders with different clinical presentations and severity determined by mutations in the gene DMD, which encodes the sarcolemmal protein dystrophin. Diagnosis is based on clinical aspects and muscle protein analysis, followed by molecular confirmation. We revised the main aspects of the natural history of dystrophinopathies to define genotype-phenotype correlations in large patient cohorts with extended follow-up. We also specifically explored subjects carrying nucleotide substitutions in the DMD gene, a comparatively less investigated DMD/BMD subgroup. We studied 320 dystrophinopathic patients (205 DMD and 115 BMD), defining muscular, cardiac, respiratory, and cognitive involvement. We also subdivided patients according to the kind of molecular defect (deletions, duplications, nucleotide substitutions or other microrearrangements) and the mutation sites (proximal/distal to exon 45), studying phenotype-genotype correlations for each group. In DMD, mutation type did not influence clinical evolution; mutations located in distal regions (irrespective of their nature) are more likely to be associated with lower IQ levels (p=0.005). BMD carrying proximal deletions showed a higher degree of cardiac impairment than BMD with distal deletions (p=0.0046). In the BMD population, there was a strong correlation between the entity of muscle dystrophin deficiency and clinical course (p=0.002). An accurate knowledge of natural history may help in the clinical management of patients. Furthermore, several clinical trials are ongoing or are currently planned, some of which aim to target specific DMD mutations: a robust natural history is therefore essential to correctly design these experimental trials. Springer-Verlag, 2011 Duchenne muscular dystrophy nationallicence Becker muscular dystrophy nationallicence Dystrophin gene sequencing nationallicence Protein analysis nationallicence Cardiac involvement in DMD and BMD nationallicence Respiratory involvement in DMD and BMD nationallicence Magri Francesca Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Govoni Alessandra Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut D'Angelo Maria Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut Del Bo Roberto Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Ghezzi Serena Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Sandra Gandossini Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut Turconi Anna Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut Sciacco Monica Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Ciscato Patrizia Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Bordoni Andreina Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Tedeschi Silvana Laboratory of Medical Genetics, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore, Policlinico, Milan, Italy aut Fortunato Francesco Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Lucchini Valeria Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Bonato Sara Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut Lamperti Costanza Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Coviello Domenico Laboratory of Medical Genetics, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore, Policlinico, Milan, Italy aut Torrente Yvan Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Corti Stefania Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Moggio Maurizio Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Bresolin Nereo Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Comi Giacomo Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut Journal of Neurology Springer-Verlag 258/9(2011-09-01), 1610-1623 0340-5354 258:9<1610 2011 258 415 https://doi.org/10.1007/s00415-011-5979-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-011-5979-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Magri Francesca Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Govoni Alessandra Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- D'Angelo Maria Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut NATIONALLICENCE 700 1- Del Bo Roberto Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Ghezzi Serena Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Sandra Gandossini Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut NATIONALLICENCE 700 1- Turconi Anna Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut NATIONALLICENCE 700 1- Sciacco Monica Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Ciscato Patrizia Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Bordoni Andreina Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Tedeschi Silvana Laboratory of Medical Genetics, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore, Policlinico, Milan, Italy aut NATIONALLICENCE 700 1- Fortunato Francesco Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Lucchini Valeria Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Bonato Sara Scientific Institute IRCCS E. Medea, Bosisio Parini, Lecco, Italy aut NATIONALLICENCE 700 1- Lamperti Costanza Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Coviello Domenico Laboratory of Medical Genetics, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore, Policlinico, Milan, Italy aut NATIONALLICENCE 700 1- Torrente Yvan Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Corti Stefania Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Moggio Maurizio Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Bresolin Nereo Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 700 1- Comi Giacomo Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, I.R.C.C.S. Foundation Ca' Granda, Ospedale Maggiore Policlinico, Padiglione Ponti, Via Francesco Sforza 35, 20122, Milan, Italy aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/9(2011-09-01), 1610-1623 0340-5354 258:9<1610 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer