title: Photoreceptor function in heterozygotes with insertion or deletion mutations in the RDS gene.
abstract: OBJECTIVE
  To understand the pathophysiology of human retinal degenerations caused by mutations in the peripherin/RDS gene.
  
  
  METHODS
  Three families with autosomal dominant retinal degeneration were found to have mutations in the peripherin/RDS gene. There were two frameshift mutations: a 1-base pair (bp) insertion at codon 32 and a 2-bp deletion at codon 193. For these mutations, the predicted proteins would be truncated by 303 and 131 amino acids, respectively. The third mutation would result in an 8-bp substitution for five nucleotides involving codons 67-69 and would be predicted to disrupt the second transmembrane domain of the protein. Heterozygotes were examined clinically and with rod and cone perimetry, dark adaptometry, and rod- and cone-isolated electroretinograms (ERGs).
  
  
  RESULTS
  Rod and cone sensitivity losses were present with perimetric testing in most patients; patients with advanced disease in all three families showed more pericentral than peripheral field dysfunction. The kinetics of dark adaptation were abnormal in all patients. Rod and cone ERG a-waves were normal in maximum amplitude in three younger patients but were reduced in all others; phototransduction was normal in most patients. There was equal loss of rod and cone a-wave amplitudes and equal elevation of rod and cone thresholds.
  
  
  CONCLUSIONS
  Heterozygotes with these different peripherin/RDS gene mutations showed variation in clinical presentation but a similar pattern of receptor abnormalities. Results of visual function tests were consistent with a normal amount of rod and cone outer segment membrane in early disease, progressing to reduced outer segments at later stages. There was an equal effect on rod and cone photoreceptor function at all stages of disease. This functional phenotype may represent the human analogue of the rds/+ mouse.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania School of Medicine, Scheie Eye Institute, Philadelphia 19104, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: A V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: C M
authors.initials: CM
authors.lastname: Kemp
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins; D010375:Pedigree; D064531:Peripherins; D010786:Photoreceptor Cells / Q000502:physiology / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology*; D017384:Sequence Deletion; D015398:Signal Transduction; D058609:Visual Field Tests
chemical_list: D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; C578996:Prph2 protein, mouse; D004247:DNA