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Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene

  • Clinical Investigation
  • Published:
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Abstract

Purpose

To identify the genetic defect, and to phenotype, three consanguineous Tunisian families presenting with early-onset retinal degeneration (EORD).

Methods

All accessible family members were included. They underwent blood sampling and ophthalmological examination including, when possible, full-field ERG and pupillometry. A genome-wide linkage analysis was initiated. Mutation analysis of the RPE65 gene within the linked interval was performed by bi-directional sequencing.

Results

Eleven out of 53 examined members were clinically affected with an EORD. Linkage analysis revealed a maximal lod score of 4.02 (θ=0.1) for the marker D1S207 on 1p31. Mutational screening of the RPE65 gene identified a homozygous R91W mutation co-segregating with the disease in all affected individuals. Eleven homozygotes had nystagmus and acuities ranging from CF to NLP. Two retinal patterns were identified: pattern 1 presented mid-peripheral deep white dot deposits and virtually no clumped pigmentation, whereas pattern 2 showed mid-peripheral pigmented clumps without any white deposits. Homozygotes had no detectable full-field ERG and an abnormal pupillary light reflex. Eleven heterozygotes had normal visual function.

Conclusion

We identified and characterised an endemic form of early onset rod-cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single RPE65 mutation. Two funduscopic patterns were identified: white dot deposits in earlier stages and clumped pigment in later stages.

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Notes

  1. Moiseyev et al identified the RPE65 protein as the isomerohydrolase transforming all‐trans retinyl‐ester into 11‐cis retinol. Moiseyev G, Chen Y, Takahashi Y, Wu BX, Ma JX. RPE65 is the isomerohydrolase in the retinoid visual cycle. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12412–12418

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Acknowledgements

RPE65 Study Group: Olfa Charfi, Corinne Kostic, Karim Baglouti, Leonidas Zografos. O.C. and K.B. are from the Hedi Rais Institute of Ophthalmology, Tunis, Tunisia; Y.A. , C.K. and L.Z. from the Department of Ophthalmology, Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.

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Authors and Affiliations

  1. Hedi Rais Institute of Ophthalmology, Tunis, Tunisia

    Leila El Matri

  2. Department of Ophthalmology, Jules Gonin Eye Hospital, University of Lausanne, 1004, Lausanne, Switzerland

    Aude Ambresin, Daniel F. Schorderet, Aki Kawasaki, Yvan Arsenijevic, François‐Xavier Borruat & Francis L. Munier

  3. Institut de Recherche en Ophtalmologie, Sion, Switzerland

    Daniel F. Schorderet

  4. Retinal Electrodiagnostics Research Group, Department of Ophthalmology, University of Tübingen, Tübingen, Germany

    Mathias W. Seeliger

  5. Opthalmology, Retinal Cell Biology, University Hospital of Zurich, Zurich, Switzerland

    Andreas Wenzel

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  1. Leila El Matri
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  2. Aude Ambresin
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Corresponding authors

Correspondence to Aude Ambresin or Francis L. Munier.

Additional information

L. El Matri and A. Ambresin contributed equally to this work.

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El Matri, L., Ambresin, A., Schorderet, D.F. et al. Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene. Graefe's Arch Clin Exp Ophthalmo 244, 1104–1112 (2006). https://doi.org/10.1007/s00417-005-0096-2

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  • DOI: https://doi.org/10.1007/s00417-005-0096-2

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