Human Genetics

, Volume 96, Issue 2, pp 167–176 | Cite as

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

  • Jorge Azofeifa
  • Thomas Voit
  • Christoph Hübner
  • Marion Cremer
Original Investigation


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 M27β (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 ≥90% of their peripheral lymphocytes was observed, two cases showed non-appparent 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.


Restriction Fragment Length Polymorphism Muscular Dystrophy Duchenne Muscular Dystrophy Activation Ratio Normal Karyotype 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Jorge Azofeifa
    • 1
  • Thomas Voit
    • 2
  • Christoph Hübner
    • 3
  • Marion Cremer
    • 1
  1. 1.Institut für Humangenetik und Anthropologie der Universität HeidelbergHeidelbergGermany
  2. 2.UniversitätskinderklinikDüsseldorfGermany
  3. 3.UniversitätskinderklinikCharité, BerlinGermany

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