Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up

Francesca Magri, Alessandra Govoni, Maria Grazia D'Angelo, Roberto Del Bo, Serena Ghezzi, Gandossini Sandra, Anna Carla 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 BresolinGiacomo Pietro Comi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1610-1623
Number of pages14
JournalJournal of Neurology
Issue number9
Publication statusPublished - Sep 2011


  • Becker muscular dystrophy
  • Cardiac involvement in DMD and BMD
  • Duchenne muscular dystrophy
  • Dystrophin gene sequencing
  • Protein analysis
  • Respiratory involvement in DMD and BMD

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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