Hybridization analysis of D4Z4 repeat arrays linked to FSHD

Chromosoma. 2007 Apr;116(2):107-16. doi: 10.1007/s00412-006-0080-6. Epub 2006 Nov 28.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence / genetics*
  • Cell Line
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 4 / genetics*
  • Cricetinae
  • Cricetulus
  • DNA Primers
  • DNA Probes / genetics
  • Electrophoresis
  • Gene Components
  • Humans
  • Immunoblotting
  • Molecular Diagnostic Techniques / methods
  • Muscular Dystrophy, Facioscapulohumeral / genetics*
  • Netherlands
  • Nucleic Acid Hybridization / methods
  • Sequence Deletion / genetics*
  • Tandem Repeat Sequences / genetics*


  • DNA Primers
  • DNA Probes