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Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy

Graefe's Archive for Clinical and Experimental Ophthalmology volume 244, pages 1453–1466 (2006)Cite this article

Abstract

Aim

Longitudinal course and genotype-phenotype correlation in patients and carriers with heterozygous mutations in hBEST1 (bestrophin).

Methods

Thirteen patients and seven possible carriers were characterised by mutation analysis with SSCPA and direct sequencing, clinical examination and fundus autofluorescence (AF). Electrophysiology (EOG and mfERG) and optical coherence tomography (OCT) were additionally performed whenever possible.

Results

We identified seven different heterozygous mutations in ten unrelated families with Best disease. I296del was the most frequent mutation. Five of nine individuals with I295del and two of three with N99K were asymptomatic carriers. One patient with I295del mutation had funduscopically unilateral Best disease. In three children (all with I295del), EOG initially showed a clearly present light peak that deteriorated during 5 years of follow-up in two of them. Increased AF corresponded well to funduscopically visible lesions. During 3–6 years of follow-up, the lesion area did not change significantly, but there were obvious changes in the inner structure of the lesion.

Conclusion

In the present series I295del, the most frequent mutation in our study, and N99K showed reduced penetrance. EOG was normal in young patients even if prime signs were visible. The lesion area did not depend on the mutation and did not correlate with VA. Lower VA was associated with a more irregular AF pattern due to scarring or haemorrhage. Our results indicate a disease causing effect that is cumulative over time.

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Acknowledgements

This study was supported by grants from Deutsche Forschungsgemeinschaft (DFG Lo 457/3, DFG Lo457/5). The authors would like to thank all patients and their families for participating in the study, Christoph Friedburg, MD for fruitful discussions on electrophysiological recordings, Renate Foeckler for excellent technical assistance, Martin Rosner, Roman Miedl and Günther Schuch for OCT, fundus and AF imaging and Birgit Langer and Ulla Biendl for electrophysiological recordings.

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Author notes

  1. B. Wabbels

    Present address: Department of Ophthalmology, University of Bonn, Klinikum, Abbestr. 2, 53127, Bonn, Germany

Authors and Affiliations

  1. Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics, University of Regensburg, Klinikum, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany

    B. Wabbels, M. N. Preising, U. Kretschmann, A. Demmler & B. Lorenz

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  1. B. Wabbels
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  2. M. N. Preising
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  3. U. Kretschmann
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  4. A. Demmler
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  5. B. Lorenz
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Corresponding author

Correspondence to M. N. Preising.

Additional information

B. Wabbels and M. N. Preising contributed equally in this work.

Proprietary Interest Statement: The authors do not have any financial interest in the methods or equipment reported in this manuscript.

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Wabbels, B., Preising, M.N., Kretschmann, U. et al. Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy. Graefe's Arch Clin Exp Ophthalmo 244, 1453–1466 (2006). https://doi.org/10.1007/s00417-006-0286-6

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  • DOI: https://doi.org/10.1007/s00417-006-0286-6

Keywords

  • Bestrophin
  • Juvenile vitelliform macular dystrophy
  • Longitudinal course
  • Optical coherence tomography
  • Electrooculogram
  • Fundus autofluorescence