title: BEST1 sequence variants in Italian patients with vitelliform macular dystrophy.
abstract: OBJECTIVE
  To analyze the spectrum of sequence variants in the BEST1 gene in a group of Italian patients affected by Best vitelliform macular dystrophy (VMD).
  
  
  METHODS
  Thirty Italian patients with a diagnosis of VMD and 20 clinically healthy relatives were recruited. They belonged to 19 Italian families predominantly originating from central Italy. They received a standard ophthalmologic examination, OCT scan, and electrophysiological tests (ERG and EOG). Fluorescein and ICG angiographies and fundus autofluorescence imaging were performed in selected cases. DNA samples were analyzed for sequence variants of the BEST1 gene by direct sequencing techniques.
  
  
  RESULTS
  Nine missense variants and one deletion were found in the affected patients; each patient carried one mutation. Five variants [c.73C>T (p.Arg25Trp), c.652C>T (p.Arg218Cys), c.652C>G (p.Arg218Gly), c.728C>T (p.Ala243Val), c.893T>C (p.Phe298Ser)] have already been described in literature while another five variants [c.217A>C (p.Ile73Leu), c.239T>G (p.Phe80Cys), c.883_885del (p.Ile295del), c.907G>A (p.Asp303Asn), c.911A>G (p.Asp304Gly)] had not previously been reported. Affected patients, sometimes even from the same family, occasionally showed variable phenotypes. One heterozygous variant was also found in five clinically healthy relatives with normal fundus, visual acuity and ERG but with abnormal EOG.
  
  
  CONCLUSIONS
  Ten variants in the BEST1 gene were detected in a group of individuals with clinically apparent VMD, and in some clinically normal individuals with an abnormal EOG. The high prevalence of novel variants and the frequent report of a specific variant (p.Arg25Trp) that has rarely been described in other ethnic groups suggests a distribution of BEST1 variants peculiar to Italian VMD patients.
authors.affiliation: Department of Specialized Surgical Sciences, Eye Clinic, University of Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sodi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Passerini
authors.forename: Vittoria
authors.initials: V
authors.lastname: Murro
authors.forename: Roberto
authors.initials: R
authors.lastname: Caputo
authors.forename: Giacomo Maria
authors.initials: GM
authors.lastname: Bacci
authors.forename: Mirela
authors.initials: M
authors.lastname: Bodoj
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
authors.forename: Ugo
authors.initials: U
authors.lastname: Menchini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000075002:Bestrophins; D016022:Case-Control Studies; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D057826:Vitelliform Macular Dystrophy / Q000235:genetics*
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins