Human Genetics

, Volume 105, Issue 1, pp 2–9

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

Authors

  • De-Ann M. Pillers
    • Department of Pediatrics, NRC-5, Oregon Child Health Research Center, Doernbecher Children's Hospital, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201–3042
  • K.M. Fitzgerald
    • Section of Genetics, University of Missouri School of Medicine, Kansas City, Mo.
  • N.M. Duncan
    • Department of Pediatrics, NRC-5, Oregon Child Health Research Center, Doernbecher Children's Hospital, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201–3042
  • S.M. Rash
    • Department of Pediatrics, NRC-5, Oregon Child Health Research Center, Doernbecher Children's Hospital, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201–3042
  • R.A. White
    • Section of Genetics, University of Missouri School of Medicine, Kansas City, Mo.
  • S.J. Dwinnell
    • Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Ore.
  • B.R. Powell
    • Kapiolani Medical Center for Women and Children, Honolulu, Hawaii
  • R.E. Schnur
    • The Children's Regional Hospital, Cooper Hospital/University of Medicine and Dentistry of New Jersey, Camden, N.J.
  • P.N. Ray
    • Departments of Genetics, Research Institute and Pediatric Laboratory Medicine, Hospital for Sick Children, and the Department of Molecular and Medical Genetics, University of Toronto, Ontario
  • G.W. Cibis
    • Section of Ophthalmology, University of Missouri School of Medicine, Kansas City, Mo.
  • R.G. Weleber
    • Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Ore.
Original Investigation

DOI: 10.1007/s004399900111

Cite this article as:
Pillers, D., Fitzgerald, K., Duncan, N. et al. Hum Genet (1999) 105: 2. doi:10.1007/s004399900111

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.

Copyright information

© Springer-Verlag 1999