title: 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.
abstract: 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.
authors.affiliation: Institut für Humangenetik und Anthropologie, Universität Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Azofeifa
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: C
authors.initials: C
authors.lastname: Hübner
authors.forename: M
authors.initials: M
authors.lastname: Cremer
mesh_terms: D002648:Child; D004247:DNA / Q000737:chemistry*; D003627:Data Interpretation, Statistical; D004303:Dosage Compensation, Genetic; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008745:Methylation; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D014960:X Chromosome / Q000235:genetics*
chemical_list: D016189:Dystrophin; D004247:DNA