May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Genotype Phenotype Correlations in Patients With OPA1 DNA Sequence Variants
Author Affiliations & Notes
  • D.R. Figueiredo
    Ophthalmology, Harvard Medical School, Boston, MA
  • L.R. Pasquale
    Ophthalmology, Harvard Medical School, Boston, MA
  • S. Wagner
    Ophthalmology, Harvard Medical School, Boston, MA
  • E. DelBono
    Ophthalmology, Harvard Medical School, Boston, MA
  • J.L. Haines
    Center for Human Genetic Research, Vanderbilt School of Medicine, Nashville, TN
  • J.L. Wiggs
    Ophthalmology, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships  D.R. Figueiredo, None; L.R. Pasquale, None; S. Wagner, None; E. DelBono, None; J.L. Haines, None; J.L. Wiggs, None.
  • Footnotes
    Support  NIH Grant EY015872, P30 EY014104
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4612. doi:
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      D.R. Figueiredo, L.R. Pasquale, S. Wagner, E. DelBono, J.L. Haines, J.L. Wiggs; Genotype Phenotype Correlations in Patients With OPA1 DNA Sequence Variants . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4612.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : OPA1 codes for a dynamin–related GTPase that functions in mitochondria. The protein is expressed in retinal ganglion cells as well as many other tissues. OPA1 DNA sequence changes have been identified in patients with a wide range of phenotypes including autosomal dominant optic atrophy, low tension glaucoma and a syndrome of optic atrophy and sensorineural hearing loss. The purpose of this study is to describe the clinical characteristics of patients with optic nerve disease and OPA1 DNA sequence variants.

Methods: : 80 low tension glaucoma patients, 130 high tension glaucoma patients, 8 members of a family affected by an autosomal dominant form of optic atrophy and 80 controls patients were screened for OPA1 DNA sequence variants by direct genomic sequencing of all 29 exons and flanking introns of the OPA1 gene. Low tension glaucoma was defined as optic nerve damage with corresponding visual field changes in at least one eye, and intraocular pressure (IOP) less than 22 mmHg, and high pressure glaucoma met the same optic nerve criteria, but with IOP greater than 22 mmHg.

Results: : In low tension glaucoma patients, two novel missense changes (Thr95Met, Lys582Arg) and one previously identified nonsynonymous SNP (Ser158Asn) was found. The Thr95Met and Lys582Arg variants were not present in the high tension glaucoma patients or controls. A novel nonsense mutation R612X was found in the proband and all affected members of the optic atrophy family. Variable expressivity of the optic nerve dysfunction was observed among family members. Although the previously studied IVS 8+4 C>T and IVS 8+10 T>C polymorphisms were identified in these patient populations, an association between these DNA sequence changes and optic nerve disease was not found. We did not find the R445H mutation associated with optic atrophy and sensisorneural hearing loss in any patient in this population.

Conclusions: : Patients with optic atrophy and low tension glaucoma have similar clinical characteristics suggesting that they may have common etiologies. Mitochrondrial dysfunction has been shown to be a component of Kjer’s autosomal dominant optic atrophy and Leber’s hereditary optic atrophy. OPA1 mutations associated with dominant optic atrophy may cause loss of protein function, while missense mutations associated with low tension glaucoma may have a less profound effect on the protein activity. Further characterization of the clinical phenotypes of patients with forms of optic atrophy and OPA1 mutations will be necessary to confirm this hypothesis.

Keywords: gene screening • optic disc • neuro-ophthalmology: optic nerve 

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