Duchenne/Becker muscular dystrophy: Correlation of phenotype by electroretinography with sites of dystrophin mutations

De Ann M. Pillers, Kathleen M. Fitzgerald, Nancy M. Duncan, Sean M. Rash, Robert A. White, Shannon J. Dwinnell, Berkley R. Powell, Rhonda E. Schnur, Peter N. Ray, Gerhard W. Cibis, Richard G. Weleber

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The dark-adapted electroretinogram (ERG) of patients with Duchenne and Becker muscular dystrophy (DMD/BMD) shows a marked reduction in b-wave amplitude. Genotype-phenotype studies of mouse models for DMD show position-specific effects of the mutations upon the phenotype: mice with 5' defects of dystrophin have normal ERGs, those with defects in the central region have a normal b-wave amplitude associated with prolonged implicit times for both the b-wave and oscillatory potentials, and mice with 3' defects have a phenotype similar to that seen in DMD/BMD patients. The mouse studies suggest a key role for the carboxyl terminal dystrophin isoform, Dp260, in retinal electrophysiology. We have undertaken a systematic evaluation of DMD/BMD patients through clinical examination and review of the literature in order to determine whether the position-specific effects of mutations noted in the mouse are present in man. We have found that, in man, a wider variation of DMD defects correlate with reductions in the b-wave amplitude. Individuals with normal ERGs have mutations predominantly located 5' of the transcript initiation site of Dp260. Our results suggest that the most important determinant in the ERG b-wave phenotype is the mutation position, rather than muscle disease severity. Forty-six per cent of patients with mutations 5' of the Dp260 transcript start site have abnormal ERGs, as opposed to 94% with more distal mutations. The human genotype-phenotype correlations are consistent with a role for Dp260 in normal retinal electrophysiology and may also reflect the expression of other C-terminal dystrophin isoforms and their contributions to retinal signal transmission.

Original languageEnglish (US)
Pages (from-to)2-9
Number of pages8
JournalHuman genetics
Volume105
Issue number1-2
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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