Exon deletion patterns of the dystrophin gene in 82 Vietnamese Duchenne/Becker muscular dystrophy patients

J Neurogenet. 2013 Dec;27(4):170-5. doi: 10.3109/01677063.2013.830616. Epub 2013 Oct 7.

Abstract

Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common inherited muscle diseases caused by mutations in the dystrophin gene. The reading frame rule explains the genotype-phenotype relationship in DMD/BMD. In Vietnam, extensive mutation analysis has never been conducted in DMD/BMD. Here, 152 Vietnamese muscular dystrophy patients were examined for dystrophin exon deletion by amplifying 19 deletion-prone exons and deletion ends were confirmed by dystrophin cDNA analysis if necessary. The result was that 82 (54%) patients were found to have exon deletions, thus confirming exact deletion ends. A further result was that 37 patterns of deletion were classified. Deletions of exons 45-50 and 49-52 were the most common patterns identified, numbering six cases each (7.3%). The reading frame rule explained the genotype-phenotype relationship, but not five (6.1%) DMD cases. Each of five patients had deletions of exons 11-27 in common. The applicability of the therapy producing semifunctional in frame mRNA in DMD by inducing skipping of a single exon was examined. Induction of exon 51 skipping was ranked at top priority, since 16 (27%) patients were predicted to have semifunctional mRNA skipping. Exons 45 and 53 were the next ranked, with 12 (20%) and 11 (18%) patients, respectively. The largest deletion database of the dystrophin gene, established in Vietnamese DMD/BMD patients, disclosed a strong indication for exon-skipping therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Asian People / genetics
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Dystrophin / genetics*
  • Exons
  • Gene Deletion
  • Genetic Therapy / methods
  • Genotype
  • Humans
  • Male
  • Multiplex Polymerase Chain Reaction
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / therapy
  • Phenotype
  • Young Adult

Substances

  • Dystrophin