Neuromuscular Disorders
Volume 20, Issue 8 , Pages 499-504 , August 2010

Clinical and genetic characterization of manifesting carriers of DMD mutations

  • Payam Soltanzadeh

      Affiliations

    • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
  • ,
  • Michael J. Friez

      Affiliations

    • Molecular Diagnostic Laboratory, Greenwood Genetic Center, Greenwood, SC, USA
  • ,
  • Diane Dunn

      Affiliations

    • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
  • ,
  • Andrew von Niederhausern

      Affiliations

    • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
  • ,
  • Olga L. Gurvich

      Affiliations

    • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
    • Present address: Cork Cancer Research Centre, BioSciences Institute, University College Cork, Cork, Ireland.
  • ,
  • Kathryn J. Swoboda

      Affiliations

    • Department of Neurology, University of Utah, Salt Lake City, UT, USA
    • Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
  • ,
  • Jacinda B. Sampson

      Affiliations

    • Department of Neurology, University of Utah, Salt Lake City, UT, USA
  • ,
  • Alan Pestronk

      Affiliations

    • Department of Neurology, Washington University, St. Louis, MO, USA
  • ,
  • Anne M. Connolly

      Affiliations

    • Department of Neurology, Washington University, St. Louis, MO, USA
  • ,
  • Julaine M. Florence

      Affiliations

    • Department of Neurology, Washington University, St. Louis, MO, USA
  • ,
  • Richard S. Finkel

      Affiliations

    • Department of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  • ,
  • Carsten G. Bönnemann

      Affiliations

    • Department of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  • ,
  • Livija Medne

      Affiliations

    • Department of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  • ,
  • Jerry R. Mendell

      Affiliations

    • Center for Gene Therapy, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University, Columbus, OH, USA
  • ,
  • Katherine D. Mathews

      Affiliations

    • Department of Pediatrics, University of Iowa, Iowa City, IA, USA
  • ,
  • Brenda L. Wong

      Affiliations

    • Departments of Neurology and Pediatrics, Cincinnati Children’s Hospital, Cincinnati, OH, USA
  • ,
  • Michael D. Sussman

      Affiliations

    • Department of Orthopedic Surgery, Shriners Hospital for Children, Portland, OR, USA
  • ,
  • Jonathan Zonana

      Affiliations

    • Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA
  • ,
  • Karen Kovak

      Affiliations

    • Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA
  • ,
  • Sidney M. Gospe Jr.

      Affiliations

    • Departments of Neurology and Pediatrics, University of Washington, Division of Pediatric Neurology, Seattle Children’s Hospital, Seattle, WA, USA
  • ,
  • Eduard Gappmaier

      Affiliations

    • Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA
  • ,
  • Laura E. Taylor

      Affiliations

    • Center for Gene Therapy, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University, Columbus, OH, USA
  • ,
  • Michael T. Howard

      Affiliations

    • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
  • ,
  • Robert B. Weiss

      Affiliations

    • Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
  • ,
  • Kevin M. Flanigan

      Affiliations

    • Center for Gene Therapy, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University, Columbus, OH, USA
    • Corresponding Author InformationCorresponding author. Address: Center for Gene Therapy, Nationwide Children’s Hospital, 700 Children’s Drive, WA4023, Columbus, OH 43205, USA. Tel.: +1 614 355 2947; fax: +1 614 722 3273.

Received 15 August 2009 ,Revised 30 April 2010 ,Accepted 18 May 2010.

References 

  1. Moser H, Emery AE. The manifesting carrier in Duchenne muscular dystrophy. Clin Genet. 1974;5:271–284
  2. Norman A, Harper P. A survey of manifesting carriers of Duchenne and Becker muscular dystrophy in Wales. Clin Genet. 1989;36:31–37
  3. Taylor PJ, Maroulis S, Mullan GL, et al. Measurement of the clinical utility of a combined mutation detection protocol in carriers of Duchenne and Becker muscular dystrophy. J Med Genet. 2007;44:368–372
  4. Arahata K, Ishihara T, Kamakura K, et al. Mosaic expression of dystrophin in symptomatic carriers of Duchenne’s muscular dystrophy. N Engl J Med. 1989;320:138–142
  5. Hoffman EP, Arahata K, Minetti C, et al. Dystrophinopathy in isolated cases of myopathy in females. Neurology. 1992;42:967–975
  6. Arikawa E, Hoffman EP, Kaido M, et al. The frequency of patients with dystrophin abnormalities in a limb-girdle patient population. Neurology. 1991;41:1491–1496
  7. Hoogerwaard EM, Ginjaar IB, Bakker E, de Visser M. Dystrophin analysis in carriers of Duchenne and Becker muscular dystrophy. Neurology. 2005;65:1984–1986
  8. Hoogerwaard EM, Bakker E, Ippel PF, et al. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study. Lancet. 1999;353:2116–2119
  9. Flanigan KM, von Niederhausern A, Dunn DM, et al. Rapid direct sequence analysis of the dystrophin gene. Am J Hum Genet. 2003;72:931–939
  10. Roberts RG, Barby TF, Manners E, et al. Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes. Am J Hum Genet. 1991;49:298–310
  11. Allen RC, Zoghbi HY, Moseley AB, et al. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet. 1992;51:1229–1239
  12. Plenge RM, Hendrich BD, Schwartz C, et al. A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation. Nat Genet. 1997;17:353–356
  13. Amos-Landgraf JM, Cottle A, Plenge RM, et al. X chromosome-inactivation patterns of 1005 phenotypically unaffected females. Am J Hum Genet. 2006;79:493–499
  14. Bushby KM, Goodship JA, Nicholson LV, et al. Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1993;3:57–64
  15. Center WUND. Dystrophinopathies: female carriers. Neuromuscular syndromes.
  16. van Essen AJ, Mulder IM, van der Vlies P, et al. Detection of point mutation in dystrophin gene reveals somatic and germline mosaicism in the mother of a patient with Duchenne muscular dystrophy. Am J Med Genet A. 2003;118A:296–298
  17. Hoogerwaard EM, van der Wouw PA, Wilde AA, et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1999;9:347–351
  18. Mirabella M, Servidei S, Manfredi G, et al. Cardiomyopathy may be the only clinical manifestation in female carriers of Duchenne muscular dystrophy. Neurology. 1993;43:2342–2345
  19. Kinoshita H, Goto Y, Ishikawa M, et al. A carrier of Duchenne muscular dystrophy with dilated cardiomyopathy but no skeletal muscle symptom. Brain Dev. 1995;17:202–205
  20. Azofeifa J, Voit T, Hubner C, Cremer M. 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;96:167–176
  21. Muntoni F, Mateddu A, Marrosu MG, et al. Variable dystrophin expression in different muscles of a Duchenne muscular dystrophy carrier. Clin Genet. 1992;42:35–38
  22. Dent KM, Dunn DM, von Niederhausern AC, et al. Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. 2005;134:295–298
  23. Matthews PM, Benjamin D, Van Bakel I, et al. Muscle X-inactivation patterns and dystrophin expression in Duchenne muscular dystrophy carriers. Neuromuscul Disord. 1995;5:209–220
  24. Bittel DC, Theodoro MF, Kibiryeva N, et al. Comparison of X-chromosome inactivation patterns in multiple tissues from human females. J Med Genet. 2008;45:309–313
  25. Bolduc V, Chagnon P, Provost S, et al. No evidence that skewing of X chromosome inactivation patterns is transmitted to offspring in humans. J Clin Invest. 2008;118:333–341
  26. Pegoraro E, Schimke RN, Arahata K, et al. Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females. Am J Hum Genet. 1994;54:989–1003
  27. Knudsen GP, Neilson TC, Pedersen J, et al. Increased skewing of X chromosome inactivation in Rett syndrome patients and their mothers. Eur J Hum Genet. 2006;14:1189–1194
  28. Plenge RM, Stevenson RA, Lubs HA, et al. Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders. Am J Hum Genet. 2002;71:168–173

PII: S0960-8966(10)00223-3

doi: 10.1016/j.nmd.2010.05.010

Neuromuscular Disorders
Volume 20, Issue 8 , Pages 499-504 , August 2010