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PMID: 7635465 Published · ppublish English Case Reports Journal Article Research Support, Non-U.S. Gov't

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.

Human genetics ·Vol. 96 ·No. 2 ·1995-08-00 ·Pages 167-76

Azofeifa J, Voit T, Hübner C, Cremer M

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.

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
Chemicals
Dystrophin DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Azofeifa J
Institut für Humangenetik und Anthropologie, Universität Heidelberg, Germany.
Voit T
Hübner C
Cremer M
References (44)
44 references, click to expand
  1. Manifesting carriers of Xp21 muscular dystrophy; lack of correlation between dystrophin expression and clinical weakness.
    Neuromuscul Disord. 1993 Mar;3(2):141-8 PMID: 8358239
  2. Mapping of X chromosome translocation breakpoints in females with Duchenne muscular dystrophy with respect to exons of the dystrophin gene.
    Hum Genet. 1992 Dec;90(4):407-12 PMID: 1483697
  3. Discordance of muscular dystrophy in monozygotic female twins: evidence supporting asymmetric splitting of the inner cell mass in a manifesting carrier of Duchenne dystrophy.
    Am J Med Genet. 1991 Sep 1;40(3):354-64 PMID: 1683155
  4. Primary non-random X-inactivation caused by controlling elements in the mouse demonstrated at the cellular level.
    Genet Res. 1982 Oct;40(2):139-47 PMID: 7152255
  5. Genomic sequencing.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 PMID: 6326095
  6. X inactivation as a mechanism of selection against lethal alleles: further investigation of incontinentia pigmenti and X linked lymphoproliferative disease.
    J Med Genet. 1992 Sep;29(9):608-14 PMID: 1404291
  7. Different patterns of X inactivation in MZ twins discordant for red-green color-vision deficiency.
    Am J Hum Genet. 1992 Aug;51(2):291-8 PMID: 1642230
  8. X-inactivation pattern in carriers of X-linked retinitis pigmentosa: a valuable means of prognostic evaluation?
    Hum Genet. 1993 Oct;92(4):359-63 PMID: 8225316
  9. Identification of novel RFLPs in the vicinity of CpG islands in Xq28: application to the analysis of the pattern of X chromosome inactivation.
    Am J Hum Genet. 1992 Jan;50(1):156-63 PMID: 1346076
  10. Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.
    Am J Med Genet. 1992 Dec 1;44(6):834-8 PMID: 1481858
  11. Evidence for preferential X-chromosome inactivation in a family with Fabry disease.
    Am J Hum Genet. 1977 Jul;29(4):361-70 PMID: 406783
  12. Isolation of genomic DNA.
    Methods Enzymol. 1987;152:180-3 PMID: 3657568
  13. X-linked Duchenne muscular dystrophy in an unusual family with manifesting carriers.
    Hum Genet. 1984;67(4):460-2 PMID: 6490012
  14. The manifesting carrier in Duchenne muscular dystrophy.
    Clin Genet. 1974;5(4):271-84 PMID: 4854942
  15. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  16. Methylation of the DXS255 hypervariable locus 5' CCGG site may be affected by factors other than X-chromosome activation status.
    Genomics. 1992 Sep;14(1):70-4 PMID: 1358800
  17. X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo.
    Nat Genet. 1993 Feb;3(2):170-4 PMID: 8499950
  18. Controlling elements in the mouse. V. Linkage tests with X-linked genes.
    Genet Res. 1981 Aug;38(1):57-70 PMID: 7024043
  19. Skewed X inactivation in a female MZ twin results in Duchenne muscular dystrophy.
    Am J Hum Genet. 1990 Apr;46(4):672-81 PMID: 2180286
  20. Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy.
    Neuromuscul Disord. 1993 Jan;3(1):57-64 PMID: 8329890
  21. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome.
    Nature. 1991 Jan 3;349(6304):38-44 PMID: 1985261
  22. Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency).
    Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):39-42 PMID: 1986380
  23. Differential methylation of the hypervariable locus DXS255 on active and inactive X chromosomes correlates with the expression of a human X-linked gene.
    Genomics. 1990 Jun;7(2):215-21 PMID: 2347586
  24. An informative polymorphism detectable by polymerase chain reaction at the 3' end of the dystrophin gene.
    Hum Genet. 1990 Feb;84(3):283-5 PMID: 1968037
  25. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):623-7 PMID: 1731332
  26. Skewed inactivation of an X chromosome deleted at the dystrophin gene in an asymptomatic mother and her affected daughter.
    Hum Genet. 1994 May;93(5):563-7 PMID: 8168835
  27. Primordial cell pool size and lineage relationships of five human cell types.
    Ann Hum Genet. 1973 Jul;37(1):39-48 PMID: 4759903
  28. Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation.
    N Engl J Med. 1987 Feb 19;316(8):427-31 PMID: 2880293
  29. The hypervariable DXS255 locus contains a LINE-1 repetitive element with a CpG island that is extensively methylated only on the active X chromosome.
    Genomics. 1992 Nov;14(3):598-603 PMID: 1385307
  30. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors.
    Science. 1985 Feb 8;227(4687):642-5 PMID: 2982210
  31. Muscular dystrophy in young girls.
    Neurology. 1970 Feb;20(2):147-59 PMID: 5460703
  32. Investigation of a female manifesting Becker muscular dystrophy.
    J Med Genet. 1992 Aug;29(8):578-82 PMID: 1518025
  33. X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.
    Am J Hum Genet. 1992 Nov;51(5):1136-49 PMID: 1415255
  34. Maximum-likelihood analysis of human T-cell X chromosome inactivation patterns: normal women versus carriers of X-linked severe combined immunodeficiency.
    Am J Hum Genet. 1992 Apr;50(4):742-8 PMID: 1550118
  35. Direct visualization of the dystrophin network on skeletal muscle fiber membrane.
    J Cell Biol. 1992 Dec;119(5):1183-91 PMID: 1447296
  36. Mammalian X-chromosome inactivation and the XIST gene.
    Curr Opin Genet Dev. 1992 Jun;2(3):439-47 PMID: 1504619
  37. Methylation patterns at the hypervariable X-chromosome locus DXS255 (M27 beta): correlation with X-inactivation status.
    Genomics. 1990 Jun;7(2):182-7 PMID: 1693357
  38. MUSCULAR DYSTROPHY (DUCHENNE) IN A GIRL WITH TURNER'S SYNDROME.
    J Med Genet. 1965 Mar;2(1):38-46 PMID: 14296923
  39. Female haemophilia A in a family with seeming extreme bidirectional lyonization tendency: abnormal premature X-chromosome inactivation?
    Clin Genet. 1989 Jan;35(1):41-8 PMID: 2564325
  40. Rapid detection of CA polymorphisms in cloned DNA: application to the 5' region of the dystrophin gene.
    Am J Hum Genet. 1991 Mar;48(3):621-7 PMID: 1998344
  41. Xp21 dystrophin and 6q dystrophin-related protein. Comparative immunolocalization using multiple antibodies.
    Am J Pathol. 1991 Nov;139(5):969-76 PMID: 1951635
  42. Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females.
    Am J Hum Genet. 1994 Jun;54(6):989-1003 PMID: 8198142
  43. Mechanisms of X-chromosome regulation.
    Annu Rev Genet. 1988;22:199-233 PMID: 3071248
  44. CpG-rich islands and the function of DNA methylation.
    Nature. 1986 May 15-21;321(6067):209-13 PMID: 2423876
Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
0340-6717
DOI
10.1007/BF00207374
Published
1995-08-00
Pages
167-76
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00207374 View journal details
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