December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Incomplete Penetrance in Large Autosomal Dominant Optic Atrophy Pedigrees
Author Affiliations & Notes
  • JE Craig
    Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital Melbourne Australia
  • NJ Marchbank
    Molecular Medicine Unit University of Leeds Leeds United Kingdom
  • C Toomes
    Molecular Medicine Unit University of Leeds Leeds United Kingdom
  • DL Healey
    Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital Melbourne Australia
  • KM Rattray
    Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital Melbourne Australia
  • M Toohey
    Ballarat Eye Clinic Ballarat Australia
  • P McCartney
    Ophthalmology Royal Hobart Hospital Hobart Australia
  • AJ Churchill
    Ophthalmology Bristol Eye Hospital Bristol United Kingdom
  • CF Inglehearn
    Molecular Medicine Unit University of Leeds Leeds United Kingdom
  • DA Mackey
    Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital Melbourne Australia
  • Footnotes
    Commercial Relationships   J.E. Craig, None; N.J. Marchbank, None; C. Toomes, None; D.L. Healey, None; K.M. Rattray, None; M. Toohey, None; P. McCartney, None; A.J. Churchill, None; C.F. Inglehearn, None; D.A. Mackey, None.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 907. doi:
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      JE Craig, NJ Marchbank, C Toomes, DL Healey, KM Rattray, M Toohey, P McCartney, AJ Churchill, CF Inglehearn, DA Mackey; Incomplete Penetrance in Large Autosomal Dominant Optic Atrophy Pedigrees . Invest. Ophthalmol. Vis. Sci. 2002;43(13):907.

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

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Abstract

Abstract: : Purpose: The gene mutated in autosomal dominant optic atrophy (ADOA) linked to chromosome 3q28 (OPA1) was recently identified. Estimates of penetrance for ADOA have varied considerably. The purpose of this study was to investigate penetrance in two large multi-generational pedigrees with established OPA1 mutations. Methods: Two large pedigrees with typical clinical features of ADOA were ascertained in South-Eastern Australia (ADOA Vic1, and ADOA Tas4). Linkage to OPA1 on chromosome 3q28 was confirmed. Identification of the responsible mutations in OPA1 enabled a formal study of penetrance by the attempted ascertainment of all mutation carrying individuals. Examples of incomplete penetrance were noted in each pedigree. Pedigree members were examined and findings documented (visual acuity, color vision, automated perimetry and stereo disc photos). Results: Clinical examination has been performed in 14 individuals carrying a 560-860 kb deletion encompassing the entire OPA1 gene in pedigree ADOA Vic1, and in 29 individuals carrying a 4bp deletion in exon 27, 2708del(TTAG) in pedigree ADOA Tas4. Combined results for Snellen visual acuity (VA) are presented for 43 mutation carriers. 11/43 (25.6%) had VA 20/20 or better in both eyes (mostly with normal color vision, automated perimetry and disc appearance). 22/43 (51.2%) maintained sufficient VA to hold a driving license. 30/43 (69.8%) had VA worse than 20/20 but better than or equal to 20/200. 2/43 individuals (4.7%) were legally blind (VA worse than 20/200). Conclusion: A significant percentage of carriers of OPA1 mutations are asymptomatic and have normal or better than average VA. We have observed slow progression with age. Ascertainment of all individuals in these pedigrees known to be affected has been completed. We expect penetrance levels to fall as further unaffected carriers are ascertained and are currently investigating the determinants of disease severity.

Keywords: 420 genetics • 487 neuro-ophthalmology: optic nerve • 498 optic disc 
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