X-chromosome methylation in manifesting and healthy carriers of dystrophinopathies: concordance of activation ratios among first degree female relatives and skewed inactivation as cause of the affected phenotypes

Hum Genet. 1995 Aug;96(2):167-76. doi: 10.1007/BF00207374.


The X-chromosome activity states of 11 manifesting carriers of dystrophinopathies, all with normal karyotypes, were estimated by restriction fragment length polymorphism (RFLP)-methylation analysis with the probes M27 beta (DXS255), p2-19(DXS605) and pSPT/PGK (PGK1) to test the role of skewed X-inactivation ratios as the cause of their affected phenotypes. In eight cases preferential inactivation of the putative X chromosome carrying the normal dystrophin allele in > or = 90% of their peripheral lymphocytes was observed, two cases showed non-apparent deviant ratios (60:40 and 70:30) from the theoretically expected values around the mean of 50% and in one case the three markers employed yielded no information. The analysis of the X-inactivation ratio in six mother-daughter pairs, all non-manifesting Duchenne muscular dystrophy (DMD) carriers, and in the close female relatives of the patients showed: (a) neither of the two X chromosomes was preferentially inactivated with respect to their parental origin; (b) a high concordance among the activation ratios of mothers and daughters, a result difficult to explain just in terms of random X-chromosome inactivation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • DNA / chemistry*
  • Data Interpretation, Statistical
  • Dosage Compensation, Genetic*
  • Dystrophin / genetics*
  • Female
  • Heterozygote*
  • Humans
  • Infant
  • Male
  • Methylation
  • Muscular Dystrophies / genetics*
  • Pedigree
  • Polymorphism, Restriction Fragment Length
  • X Chromosome / genetics*


  • Dystrophin
  • DNA