title: OPA1 mutations associated with dominant optic atrophy influence optic nerve head size.
abstract: OBJECTIVE
  To analyze the influence of OPA1 gene mutations on the optic nerve head (ONH) morphology in patients with dominant optic atrophy (DOA).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Twenty-eight patients with DOA from 11 pedigrees, which were positive for the presence of OPA1 gene mutations, and 56 age-matched control subjects, were enrolled.
  
  
  METHODS
  The ONH of DOA patients was studied by optical coherence tomography and compared with an age-matched control group of 56 individuals.
  
  
  METHODS
  ONH area, and vertical and horizontal diameters.
  
  
  RESULTS
  The ONH analysis of DOA patients showed a significantly smaller optic disc area (P<0.0001), vertical (P = 0.018), and horizontal (P<0.0001) disc diameters, compared with controls. Stratification of the results for the single OPA1 mutation revealed normal ONH area with 2 mutations, whereas the only missense mutation linked to a "DOA plus" phenotype had the smallest ONH measurements.
  
  
  CONCLUSIONS
  The DOA patients carrying OPA1 gene mutations present, as a group, a significantly smaller ONH compared with the range of size observed in a control population; this feature may be mutation specific. This observation suggests that OPA1 is involved in shaping the anatomic conformation of the ONH in patients with DOA. The relevance of OPA1 in regulating apoptosis and modeling the eye development has been recently shown by others. Thus, mutations in the OPA1 gene may determine the previously unrecognized feature of a smaller optic disc size and this in turn may have relevance for DOA pathogenesis. Furthermore, OPA1 gene polymorphic variants may contribute to the normal variability of ONH size in the general population.
authors.affiliation: Studio Oculistico d'Azeglio, Bologna, Italy. p.barboni@studiodazeglio.it
authors.forename: Piero
authors.initials: P
authors.lastname: Barboni
authors.forename: Michele
authors.initials: M
authors.lastname: Carbonelli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Savini
authors.forename: Beatrice
authors.initials: B
authors.lastname: Foscarini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Parisi
authors.forename: Maria L
authors.initials: ML
authors.lastname: Valentino
authors.forename: Arturo
authors.initials: A
authors.lastname: Carta
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Negri
authors.forename: Federico
authors.initials: F
authors.lastname: Sadun
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
authors.forename: Simone
authors.initials: S
authors.lastname: Schimpf
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000175:diagnosis / Q000235:genetics*; D009898:Optic Disk / Q000473:pathology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human