title: First report of OPA1 screening in Greek patients with autosomal dominant optic atrophy and identification of a previously undescribed OPA1 mutation.
abstract: OBJECTIVE
  To describe the genotype-phenotype correlation in four Greek pedigrees with autosomal dominant optic atrophy (ADOA) and OPA1 mutations.
  
  
  METHODS
  Seven patients from four unrelated families (F1, F2, F3, F4) were clinically assessed for visual acuity, color vision, ptosis, afferent pupillary defects, and visual fields and underwent orthoptic assessment, slit-lamp biomicroscopy, and fundus examination to establish their clinical status. Genomic DNA was extracted from peripheral blood samples from all participants. The coding region (exons 1-28), including the intron-exon boundaries of the OPA1 gene, was screened in the probands of the four families, as well as in seven additional family members (four affected and three unaffected) with PCR and direct DNA sequencing.
  
  
  RESULTS
  All patients presented bilateral decrease in best-corrected visual acuity and temporal pallor of the optic disc. The visual fields of the adult patients showed characteristic scotomata. Other signs were present in some patients such as decreased color discrimination and a gray crescent within the neuroretinal rim. After the OPA1 gene was sequenced, a previously undescribed heterozygous splice-site mutation c.784-1G>T in intron 7 was detected in family F2. In families F1, F3, and F4, a previously reported in-frame deletion c.876_878delTGT/p.(Val294del), the frameshift c.2366delA/p.(Asn789Metfs*11), and splice-site c.1140+5G>C mutations were detected, respectively.
  
  
  CONCLUSIONS
  This is the first report of molecular characterization of Greek patients with ADOA. Our findings provide additional information regarding the genotype-phenotype correlation and establish the role of the OPA1 gene in Greek patients with ADOA.
authors.affiliation: Ophthalmic Genetics Unit, OMMA Ophthalmological Institute of Athens, Greece.
authors.forename: Smaragda
authors.initials: S
authors.lastname: Kamakari
authors.affiliation: Ophthalmic Genetics Unit, OMMA Ophthalmological Institute of Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Koutsodontis
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Crete, Iraklion, Greece.
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Tsilimbaris
authors.affiliation: Pediatric Ophthalmology Department, MITERA Childrens' Hospital, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fitsios
authors.affiliation: Pediatric Ophthalmology Department, MITERA Childrens' Hospital, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chrousos
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005654:Fundus Oculi; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006115:Greece; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology; D009900:Optic Nerve / Q000473:pathology / Q000503:physiopathology; D014794:Visual Fields / Q000235:genetics
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human