title: Clinical and genetic heterogeneity in Slovenian patients with BEST disease.
abstract: OBJECTIVE
  To determine the spectrum of BEST1 mutations and to study the phenotype in Slovenian families with Best vitelliform macular dystrophy (BVMD) to identify genotype-phenotype correlations.
  
  
  METHODS
  Twenty patients from five families underwent the ophthalmological examination including electrooculogram (EOG; N = 17), fundus autofluorescence imaging (N = 16) and optical coherence tomography (N = 14). Mutational screening was performed by direct DNA sequencing of the BEST1 gene.
  
  
  RESULTS
  Mutation c.43G>C (p.Gly15Arg) was detected in three patients from family M presenting with different clinical stages of Best disease. Mutation c.313G>C (p.Arg105Gly) was found in families K, ST, S, B and was associated with incomplete clinical penetrance and variable retinal changes, including extramacular and multifocal lesions. In three patients from family K, an atypical form of BVMD was observed; there were additional peripheral lesions outside of the vascular arcades in addition to the typical macular lesions. Multiple alterations between the vitelliruptive and pseudohypopyon stages over a period of 11 years were seen in one patient.
  
  
  CONCLUSIONS
  Two previously unreported disease-associated variants in the BEST1 gene (p.Gly15Arg and p.Arg105Gly) were found in Slovenian patients with Best disease. Our data expand the mutation spectrum of the BEST1 gene and further support the broad phenotypic variability observed clinically and with optical coherence tomography (OCT) and AF imaging.
authors: Department of Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors: Damjan
authors: D
authors: Glavač
authors: Eye Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors: Martina
authors: M
authors: Jarc-Vidmar
authors: Department of Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors: Katarina
authors: K
authors: Vrabec
authors: Department of Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors: Metka
authors: M
authors: Ravnik-Glavač
authors: Eye Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors: Ana
authors: A
authors: Fakin
authors: Eye Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors: Marko
authors: M
authors: Hawlina
mesh_terms: D000293:Adolescent; D000328:Adult; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D061848:Optical Imaging; D010375:Pedigree; D017524:Slovenia; D041623:Tomography, Optical Coherence; D057826:Vitelliform Macular Dystrophy / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins
keywords: BEST1 gene; best vitelliform macular dystrophy; clinical phenotype; genetic eye disease; mutation detection