title: Phenotypic variability in three carriers from a family with choroideremia and a frameshift mutation 1388delCCinsG in the REP-1 gene.
abstract: OBJECTIVE
  To perform genotype-phenotype correlations in a family with choroideremia.
  
  
  METHODS
  A three-generation family with two affected males and five carriers was the subject of the study. Molecular genetic analysis using single-strand conformation polymorphism analysis (SSCP) was conducted in all subjects, while electroretinography (ERG), multifocal ERG (mfERG), scanning laser ophthalmoscope microperimetry (SLO perimetry), fluorescein angiography, and Arden contrast color testing were performed in one male and three carriers.
  
  
  RESULTS
  The findings in the affected male were typical for advanced choroideremia. The three carriers demonstrated a variable clinical phenotype including reduction of visual acuity and ERG and angiographic changes in one. Molecular genetic analysis revealed a functional null mutation (1388delCCinsG) in the REP-1 gene.
  
  
  CONCLUSIONS
  A severe retinal pathology was found in the affected male, indicating that the 1388delCCinsG is a severe mutation. Varying phenotypes were present in the three carriers examined. The phenotype in carriers has been explained by random X-inactivation with varying expression of the inactivated and activated gene copy inside the same cell of both the retinal pigment epithelium and the rods. This thesis is in agreement with the clinical data obtained here.
authors.affiliation: Kooperationsgruppe Ophthalmogenetik der LMU und GSF University Eye Hospital, LMU, München, Germany. Guenther.Rudolph@ak-i.med.uni-muenchen.de
authors.forename: Günther
authors.initials: G
authors.lastname: Rudolph
authors.forename: Markus
authors.initials: M
authors.lastname: Preising
authors.forename: Petros
authors.initials: P
authors.lastname: Kalpadakis
authors.forename: Christos
authors.initials: C
authors.lastname: Haritoglou
authors.forename: Gabriele E
authors.initials: GE
authors.lastname: Lang
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D019883:Alkyl and Aryl Transferases; D002648:Child; D015794:Choroideremia / Q000175:diagnosis / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D016368:Frameshift Mutation / Q000235:genetics*; D005654:Fundus Oculi; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014786:Vision Disorders / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity; D014794:Visual Fields; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D005136:Eye Proteins; D019883:Alkyl and Aryl Transferases; D020691:rab GTP-Binding Proteins