title: Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy.
abstract: OBJECTIVE
  To study the phenotypic characteristics of patients with a novel p.E292K mutation in BEST1.
  
  
  METHODS
  Affected individuals underwent ophthalmic examination and testing that included photography, autofluorescence, optical coherence tomography, and electrophysiological testing. Their DNA was analyzed for BEST1 mutations.
  
  
  RESULTS
  Five patients aged 5 to 59 years who expressed the p.E292K mutation in BEST1 were identified in 3 families. Electro-oculographic light-rise was subnormal in all probands and carriers. Carriers had normal findings from fundus examination, multifocal electroretinography, and visual acuity, and were emmetropic or myopic. Only probands had hyperopia and fundus findings typical of Best macular dystrophy. Optical coherence tomography of vitelliform lesions demonstrated retinal pigment epithelium elevation without subretinal fluid; atrophic lesions exhibited disruption of the hyperreflective outer retina-retinal pigment epithelium complex. Intense hyperautofluorescence correlated with the vitelliform lesion.
  
  
  CONCLUSIONS
  Patients with the Glu292Lys variation in BEST1 exhibit intrafamilial and interfamilial phenotypic variability. A disproportionate fraction (26%) of Best disease-causing mutations occurs in exon 8, suggesting that the portion of protein encoded by this exon (amino acids 290-316) may be especially important to bestrophin's function. Relatively good visual acuity with vitelliform lesions can be explained by preservation of the outer retina, demonstrated by optical coherence tomography. Clinical Relevance A novel mutation in this region of BEST1 carries implications for disease pathogenesis.
authors: Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA. elliott.sohn@gmail.com
authors: Elliott H
authors: EH
authors: Sohn
authors: Peter J
authors: PJ
authors: Francis
authors: Jacque L
authors: JL
authors: Duncan
authors: Richard G
authors: RG
authors: Weleber
authors: David A
authors: DA
authors: Saperstein
authors: Donald F
authors: DF
authors: Farrell
authors: Edwin M
authors: EM
authors: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004594:Electrophysiology; D005091:Exons / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005453:Fluorescence; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D010781:Photography; D017354:Point Mutation; D041623:Tomography, Optical Coherence
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D005973:Glutamine; D008239:Lysine