Identification of female carriers for Duchenne and Becker muscular dystrophies using a FISH-based approach

Azra H. Ligon, Catherine D. Kashork, Carolyn (Sue) Richards, Lisa G. Shaffer

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular diseases caused by dystrophin gene mutations. Deletions, or more rarely duplications, of single or multiple exons within the dystrophin gene can be detected by current molecular methods in approximately 65% of DMD patients. Mothers of affected males have a two-thirds chance of carrying a dystrophin mutation, whilst approximately one-third of affected males have de novo mutations. Currently, Southern blot analysis and multiplex PCR directed against exons in deletion hot spots are used to determine female carrier status. However, both of these assays depend on dosage assessment to accurately identify carriers since, in females, the normal X chromosome is also present. To obviate quantitation of gene dosage, we have developed exon-specific probes from the dystrophin gene and applied them to a screen for potential carrier females using fluorescence in situ hybridization (FISH). Cosmid clones, representing 16 exons, were identified and used in FISH analysis of DMD/BMD families. Our preliminary work has identified multiple, informative probes for several families with dystrophin deletions and has shown that a FISH-based assay can be an effective and direct method for establishing the DMD/BMD carrier status of females.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalEuropean Journal of Human Genetics
Volume8
Issue number4
DOIs
StatePublished - Apr 2000
Externally publishedYes

Fingerprint

Duchenne Muscular Dystrophy
Fluorescence In Situ Hybridization
Dystrophin
Exons
Mutation
Genes
Cosmids
Neuromuscular Diseases
Gene Dosage
Multiplex Polymerase Chain Reaction
X Chromosome
Southern Blotting
Clone Cells
Mothers

Keywords

  • Becker muscular dystrophy
  • Carrier detection
  • Diagnostic testing
  • Duchenne muscular dystrophy
  • FISH
  • Laboratory validation

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Identification of female carriers for Duchenne and Becker muscular dystrophies using a FISH-based approach. / Ligon, Azra H.; Kashork, Catherine D.; Richards, Carolyn (Sue); Shaffer, Lisa G.

In: European Journal of Human Genetics, Vol. 8, No. 4, 04.2000, p. 293-298.

Research output: Contribution to journalArticle

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