title: Clinical evaluation of two consanguineous families with homozygous mutations in BEST1.
abstract: OBJECTIVE
  To describe the clinical and genetic findings in two consanguineous families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations in the bestrophin-1 (BEST1) gene.
  
  
  METHODS
  Ophthalmologic examination was performed in eight members of two families originating from Spain and Denmark. Mutation screening was performed using the Vitelliform Macular Dystrophy mutation array from Asper Biotech, and by the directed genomic sequencing of BEST1.
  
  
  RESULTS
  Two homozygous mutations were detected in these families. Mutation c.936C>A (p.Asp312Glu) has been reported previously in a Danish family; here, we describe four additional individuals in this family demonstrating findings compatible with a severe dominant BVMD, albeit with reduced penetrance in heterozygotes. In the Spanish family, a novel homozygous missense mutation in exon 4, c.388 C>A (p.Arg130Ser), was identified in the siblings. Homozygous siblings demonstrated evidence of multifocal vitelliform retinopathy, whereas heterozygous family members presented findings ranging from isolated reduction of the electrooculogram Arden ratio to normal values on all clinical parameters.
  
  
  CONCLUSIONS
  As demonstrated in these consanguineous families, a great clinical variability is associated with homozygous mutations in BEST1, ranging from severe dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive bestrophinopathy.
authors: Departamento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Vigo, Spain.
authors: Teresa
authors: T
authors: Piñeiro-Gallego
authors: María
authors: M
authors: Álvarez
authors: Inés
authors: I
authors: Pereiro
authors: Severiano
authors: S
authors: Campos
authors: Dror
authors: D
authors: Sharon
authors: Patrik
authors: P
authors: Schatz
authors: Diana
authors: D
authors: Valverde
mesh_terms: D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D003241:Consanguinity; D003718:Denmark; D004585:Electrooculography; D005091:Exons; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D013030:Spain; D041623:Tomography, Optical Coherence; D057826:Vitelliform Macular Dystrophy / Q000235:genetics* / Q000473:pathology
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins