May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
A Tyr368His RPE65 Founder Mutation is Associated with a Variably Expressed Early-onset Retinal Dystrophy in 10 Families of a Genetically Isolated Population
Author Affiliations & Notes
  • S. Yzer
    Dept Human Genetics, Univ Med Ctr Nymegen, Nymegen, Netherlands
  • L.I. van den Born
    Rotterdam Eye Hospital, Rotterdam, Netherlands
  • J. Schuil
    Institute for the Visually Handicapped 'Bartimeus', Zeist, Netherlands
  • H.Y. Kroes
    Dept of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands
  • M.M. van Genderen
    Institute for the Visually Handicapped 'Bartimues', Zeist, Netherlands
  • F.N. Boonstra
    Institute for the Visually Handicapped 'Bartimeus", Zeist, Netherlands
  • B. van den Helm
    Institute for the Visually Handicapped 'Bartimeus", Zeist, Netherlands
  • H.G. Brunner
    Institute for the Visually Handicapped 'Bartimeus", Zeist, Netherlands
  • R.K. Koenekoop
    The McGill Ocular Genetics Laboratory, Montral Children's Hospital Research Institute, Montreal, PQ, Canada
  • F.P. Cremers
    The McGill Ocular Genetics Laboratory, Montral Children's Hospital Research Institute, Montreal, PQ, Canada
  • Footnotes
    Commercial Relationships  S. Yzer, None; L.I. van den Born, None; J. Schuil, None; H.Y. Kroes, None; M.M. van Genderen, None; F.N. Boonstra, None; B. van den Helm, None; H.G. Brunner, None; R.K. Koenekoop, None; F.P.M. Cremers, None.
  • Footnotes
    Support  Stichting Wetenschappelijk Onderzoek het Oogziekenhuis Rotterdam and Retina Netherlands
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1473. doi:
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      S. Yzer, L.I. van den Born, J. Schuil, H.Y. Kroes, M.M. van Genderen, F.N. Boonstra, B. van den Helm, H.G. Brunner, R.K. Koenekoop, F.P. Cremers; A Tyr368His RPE65 Founder Mutation is Associated with a Variably Expressed Early-onset Retinal Dystrophy in 10 Families of a Genetically Isolated Population . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1473.

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

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Abstract

Abstract: : Purpose: To investigate the clinical appearance and molecular cause of early onset retinal dystrophy in a genetic isolate. Methods: Fourteen patients from 10 families were examined clinically, with a mean follow-up of 9 years. Based on the observed ophthalmologic features, involvement of the RPE65 gene was suspected. Homozygosity-by-descent analysis was performed using marker D1S2803 located very near the RPE65 gene. Exons of the RPE65 gene were sequenced. Results: All patients showed moderate to severe visual acuity (VA) loss since birth indicative of an early-onset retinal dystrophy. Twelve patients of nine families are homozygous for a RPE65 1156T→C nucleotide change resulting in a Tyr368His mutation. One patient is compound heterozygous for this mutation and an IVS1+5g→a splice site mutation. One-third of patients homozygous for the Tyr368His mutation on follow-up showed a relatively stable VA, in one-third of patients VA had deteriorated, and in the remaining patients VA had improved. Three out of 96 healthy individuals from the genetic isolate and none of 92 controls from the general Dutch population were heterozygous for the Tyr368His mutation. Conclusions: Homozygosity of the Tyr368His RPE65 founder mutation is associated with congenital rod-cone dystrophy with a variable visual acuity prognosis. Based on mutation analysis and theoretical considerations, we estimate the carrier frequency in this population to be ~1 in 20 individuals rendering a significant risk of blindness in offspring of patients, their heterozygous siblings and other heterozygous individuals of the genetic isolate.

Keywords: retinal degenerations: hereditary • linkage analysis 
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