title: Ocular phenotypes associated with biallelic mutations in BEST1 in Italian patients.
abstract: OBJECTIVE
  To report on the phenotype and the genotype of Italian patients carrying BEST1 mutations on both alleles.
  
  
  METHODS
  Five Italian patients from four independent pedigrees with retinal dystrophy associated with biallelic BEST1 variants were recruited from different parts of Italy. Molecular genetic analysis of the BEST1 gene was performed with direct sequencing techniques. All the subjects included in the study were clinically evaluated with a standard ophthalmologic examination, fundus photography, optical coherence tomography scan, and electrophysiological investigations.
  
  
  RESULTS
  Six BEST1 variants were identified. Three, c.1699del (p.Glu557AsnfsX52), c.625delAAC (p.Asn179del), and c.139C>T (p.Arg47Cys), were novel, and three had already been reported in the literature, c.301C>A(p.Pro101Thr), c.934G>A (p.Asp312Asn), and c.638A>G (p.Glu213Gly). Four were missense mutations, and two were deletions. Only one BEST1 mutation was located within one of the four mutational clusters described in typical autosomal dominant Best vitelliform macular dystrophy (BVMD). Four patients showed a BVMD phenotype while one patient presented a clinical picture consistent with autosomal recessive bestrophinopathy (ARB).
  
  
  CONCLUSIONS
  Biallelic BEST1 sequence variants can be associated with at least two different phenotypes: BVMD and ARB. The phenotypic result of the molecular changes probably depends on the characteristics and the combination of the different BEST1 mutations, but unknown modifying factors such as other genes or the environment may also play a role.
authors.affiliation: Department of Specialized Surgical Sciences, Eye Clinic, University of Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sodi
authors.forename: Francesca
authors.initials: F
authors.lastname: Menchini
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Manitto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Passerini
authors.forename: Vittoria
authors.initials: V
authors.lastname: Murro
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
authors.forename: Ugo
authors.initials: U
authors.lastname: Menchini
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000075002:Bestrophins; D016022:Case-Control Studies; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D017384:Sequence Deletion; D041623:Tomography, Optical Coherence; D057826:Vitelliform Macular Dystrophy / Q000235:genetics* / Q000378:metabolism
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins