title: Duchenne/Becker muscular dystrophy: correlation of phenotype by electroretinography with sites of dystrophin mutations.
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.
authors.affiliation: Department of Pediatrics, Oregon Child Health Research Center, Doernbecher Children's Hospital, Oregon Health Sciences University, Portland 97201-3042, USA. pillersd@ohsu.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Pillers
authors.forename: K M
authors.initials: KM
authors.lastname: Fitzgerald
authors.forename: N M
authors.initials: NM
authors.lastname: Duncan
authors.forename: S M
authors.initials: SM
authors.lastname: Rash
authors.forename: R A
authors.initials: RA
authors.lastname: White
authors.forename: S J
authors.initials: SJ
authors.lastname: Dwinnell
authors.forename: B R
authors.initials: BR
authors.lastname: Powell
authors.forename: R E
authors.initials: RE
authors.lastname: Schnur
authors.forename: P N
authors.initials: PN
authors.lastname: Ray
authors.forename: G W
authors.initials: GW
authors.lastname: Cibis
authors.forename: R G
authors.initials: RG
authors.lastname: Weleber
mesh_terms: D016189:Dystrophin / Q000235:genetics*; D004596:Electroretinography; D005091:Exons; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D016189:Dystrophin; D012333:RNA, Messenger