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Keywords:

  • DMD carriers;
  • Dystrophin gene;
  • Skewed X-inactivation;
  • X-inactivation

Female carriers of Duchenne muscular dystrophy (DMD) are usually asymptomatic. However, 2.5–7.8% of them may present muscle symptoms and cardiomyopathy, attributed to a reduced production of dystrophin, probably because of skewed patterns of X-chromosome inactivation (XCI). To evaluate the role of XCI in symptomatic (at muscle or heart level) and asymptomatic DMD carriers, 44 subjects were selected from our database (12 manifesting, 21 non-manifesting, 11 healthy females), and XCI pattern determined in the lymphocytes by the androgen receptor methylation-based assay. The results showed that DMD-manifesting carriers had a preferential inactivation of the X-chromosome carrying the normal allele, while non-manifesting carriers and healthy females showed a random XCI pattern. Moreover, when comparing muscle with heart manifesting carriers, the former group showed a higher degree of skewing. No concordance in XCI was found between mothers and daughters, when symptomatic/asymptomatic mother–daughter pairs were analyzed. The results confirm that DMD clinical manifestations in carriers are associated with non-random patterns of X inactivation.