, Volume 116, Issue 2, pp 107–116 | Cite as

Hybridization analysis of D4Z4 repeat arrays linked to FSHD

  • Melanie EhrlichEmail author
  • Kesmic Jackson
  • Koji Tsumagari
  • Pilar Camaño
  • Richard J. F. L. Lemmers
Research Article


Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease involving shortening of D4Z4, an array of tandem 3.3-kb repeat units on chromosome 4. These arrays are in subtelomeric regions of 4q and 10q and have 1–100 units. FSHD is associated with an array of 1–10 units at 4q35. Unambiguous clinical diagnosis of FSHD depends on determining the array length at 4q35, usually with the array-adjacent p13E-11 probe after pulsed-field or linear gel electrophoresis. Complicating factors for molecular diagnosis of FSHD are the phenotypically neutral 10q D4Z4 arrays, cross-hybridizing sequences elsewhere in the genome, deletions including the genomic p13E-11 sequence and part of D4Z4, translocations between 4q and 10q D4Z4 arrays, and the extremely high G + C content of D4Z4 arrays (73%). In this study, we optimized conditions for molecular diagnosis of FSHD with a 1-kb D4Z4 subfragment probe after hybridization with p13E-11. We demonstrate that these hybridization conditions allow the identification of FSHD alleles with deletions of the genomic p13E-11 sequence and aid in determination of the nonpathogenic D4Z4 arrays at 10q. Furthermore, we show that the D4Z4-like sequences present elsewhere in the genome are not tandemly arranged, like those at 4q35 and 10q26.


Sodium Dodecyl Sulfate Molecular Diagnosis Acrocentric Chromosome Facioscapulohumeral Muscular Dystrophy FSHD Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Yang Fan and Chunbo Shao for help with the manuscript and Drs. Robert Bloch, Meredith Bond, and Mimi Blitzer for generously hosting us at the University of Maryland Medical School in the aftermath of the Hurricane Katrina flood in New Orleans. This research was supported in part by the National Institutes of Health, USA (NIH NS048859 to M. Ehrlich); the FSH Society (to R.J.F.L. Lemmers); and Eurogendis, Fundación Kutxa and Fundación Ilundain (to P. Camano).


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Melanie Ehrlich
    • 1
    Email author
  • Kesmic Jackson
    • 1
  • Koji Tsumagari
    • 1
  • Pilar Camaño
    • 2
  • Richard J. F. L. Lemmers
    • 3
  1. 1.Program in Human Genetics and Department of BiochemistryTulane Medical SchoolNew OrleansUSA
  2. 2.Unidad ExperimentalHospital DonostiaSan SebastiánSpain
  3. 3.Human and Clinical GeneticsLeiden University Medical CenterLeidenThe Netherlands

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