title: Genotype-phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal-dominant optic atrophy.
abstract: OBJECTIVE
  To describe the thickness of the combined ganglion cell and inner plexiform layers (GC-IPL) and the peripapillary retinal nerve fibre layer (RNFL) in patients with OPA1 c.983A>G or c.2708_2711delTTAG autosomal-dominant optic atrophy (ADOA).
  
  
  METHODS
  The study included 20 individuals with c.983A>G and nine individuals with c.2708_2711delTTAG. Data for comparison were drawn from 49, previously published, individuals with OPA1 c.2826_2836delinsGGATGCTCCA and 51 individuals with no OPA1 mutation. Subjects underwent refraction, best-corrected visual acuity assessment, axial length measurement and high-definition optical coherence tomography.
  
  
  RESULTS
  There was overlap in GC-IPL thickness in subjects younger than 20-30 years between the two new groups of ADOA patients and controls. Numerical decreases in GC-IPL thickness with age did not reach statistical significance in individuals with c.983A>G (p = 0.18) or in healthy controls (p = 0.22), but it did in individuals with c.2708_2711delTTAG (p = 0.02). Visual acuity decreased with decreasing GC-IPL thickness (p = 0.0006 in c.983A>G and p = 0.0084 in c.2708_2711delTTAG). Unlike c.2826_2836delinsGGATGCTCCA, individuals with c.983A>G or c.2708_2711delTTAG did not show a pattern of maximum GC-IPL deficit inferonasal of the fovea.
  
  
  CONCLUSIONS
  Genotype-phenotype heterogeneity in OPA1 ADOA is evident when inner retinal atrophy is examined as a function of age. Thus, a pronounced decline with age in GC-IPL thickness is observed in c.2708_2711delTTAG ADOA, an intermediate decline with age is observed in c.983A>G ADOA, whereas little or no change with age is observed in c.2826_2836delinsGGATGCTCCA ADOA. This genotype-phenotype heterogeneity may explain why some patients have progressive visual loss while others have a relatively stable prognosis.
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.|Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rönnbäck
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.|Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Nissen
authors.affiliation: Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Kennedy Center, Clinical Genetic Clinic, Copenhagen, Denmark.
authors.forename: Gitte J
authors.initials: GJ
authors.lastname: Almind
authors.affiliation: Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Kennedy Center, Clinical Genetic Clinic, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.|Singapore Eye Research Institute, Singapore National Eye Centre and Duke-NUS, Singapore, Singapore.
authors.forename: Dan
authors.initials: D
authors.lastname: Milea
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.|Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Kennedy Center, National Eye Clinic, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D058452:Axial Length, Eye / Q000473:pathology; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: autosomal-dominant optic atrophy; dominant optic atrophy; ganglion cell layer thickness; retinal nerve fibre layer thickness