Skip to main content
PMC home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 1991 Mar;75(3):147–150. doi: 10.1136/bjo.75.3.147

Genetic counselling in retinoblastoma: importance of ocular fundus examination of first degree relatives and linkage analysis.

Z Onadim 1, P G Hykin 1, J L Hungerford 1, J K Cowell 1
PMCID: PMC1042293  PMID: 2012779

Abstract

We report an unusual family pedigree segregating the retinoblastoma predisposition gene. Expression of the phenotype in different individuals in this family ranges from asymptomatic gene carriers, regressed tumours, through unifocal to bilateral multifocal lesions. Because of the unusual pattern of inheritance in this family, initial genetic counselling at a local hospital did not take into account the possibility of incomplete penetrance of the gene, and complete ophthalmological examination of unaffected family members was not undertaken. We have used DNA probes from within the retinoblastoma predisposition gene for unequivocal identification of gene carriers. The subsequent demonstration of regressed tumours in founder members of the family confirmed the diagnosis of a dominantly inherited disease. The circumstances of the management of this family emphasises the need for specialist ophthalmic examination of first degree relatives and detailed genetic analysis of all such families with DNA probes.

Full text

PDF
150

Images in this article

148Image
on p.148
148Image
on p.148
149Image
on p.149

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cavenee W. K., Hansen M. F., Nordenskjold M., Kock E., Maumenee I., Squire J. A., Phillips R. A., Gallie B. L. Genetic origin of mutations predisposing to retinoblastoma. Science. 1985 Apr 26;228(4698):501–503. doi: 10.1126/science.3983638. [DOI] [PubMed] [Google Scholar]
  2. Connolly M. J., Payne R. H., Johnson G., Gallie B. L., Allderdice P. W., Marshall W. H., Lawton R. D. Familial, EsD-linked, retinoblastoma with reduced penetrance and variable expressivity. Hum Genet. 1983;65(2):122–124. doi: 10.1007/BF00286647. [DOI] [PubMed] [Google Scholar]
  3. Cowell J. K., Jay M., Rutland P., Hungerford J. An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom. Br J Cancer. 1987 Jun;55(6):661–664. doi: 10.1038/bjc.1987.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cowell J. K., Rutland P., Jay M., Hungerford J. Deletions of the esterase D locus from a survey of 200 retinoblastoma patients. Hum Genet. 1986 Feb;72(2):164–167. doi: 10.1007/BF00283938. [DOI] [PubMed] [Google Scholar]
  5. Dunn J. M., Phillips R. A., Becker A. J., Gallie B. L. Identification of germline and somatic mutations affecting the retinoblastoma gene. Science. 1988 Sep 30;241(4874):1797–1800. doi: 10.1126/science.3175621. [DOI] [PubMed] [Google Scholar]
  6. Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
  7. Fung Y. K., Murphree A. L., T'Ang A., Qian J., Hinrichs S. H., Benedict W. F. Structural evidence for the authenticity of the human retinoblastoma gene. Science. 1987 Jun 26;236(4809):1657–1661. doi: 10.1126/science.2885916. [DOI] [PubMed] [Google Scholar]
  8. Gallie B. L., Ellsworth R. M., Abramson D. H., Phillips R. A. Retinoma: spontaneous regression of retinoblastoma or benign manifestation of the mutation? Br J Cancer. 1982 Apr;45(4):513–521. doi: 10.1038/bjc.1982.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LELE K. P., PENROSE L. S., STALLARD H. B. CHROMOSOME DELETION IN A CASE OF RETINOBLASTOMA. Ann Hum Genet. 1963 Nov;27:171–174. doi: 10.1111/j.1469-1809.1963.tb00209.x. [DOI] [PubMed] [Google Scholar]
  11. Lee W. H., Bookstein R., Hong F., Young L. J., Shew J. Y., Lee E. Y. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science. 1987 Mar 13;235(4794):1394–1399. doi: 10.1126/science.3823889. [DOI] [PubMed] [Google Scholar]
  12. Mitchell C. D., Cowell J. K. Predisposition to retinoblastoma due to a translocation within the 4.7R locus. Oncogene. 1989 Feb;4(2):253–257. [PubMed] [Google Scholar]
  13. Mitchell C., Nicolaides K., Kingston J., Hungerford J., Jay M., Cowell J. Prenatal exclusion of hereditary retinoblastoma. Lancet. 1988 Apr 9;1(8589):826–826. doi: 10.1016/s0140-6736(88)91687-x. [DOI] [PubMed] [Google Scholar]
  14. Mukai S., Rapaport J. M., Shields J. A., Augsburger J. J., Dryja T. P. Linkage of genes for human esterase D and hereditary retinoblastoma. Am J Ophthalmol. 1984 Jun;97(6):681–685. doi: 10.1016/0002-9394(84)90497-5. [DOI] [PubMed] [Google Scholar]
  15. Onadim Z. O., Mitchell C. D., Rutland P. C., Buckle B. G., Jay M., Hungerford J. L., Harper K., Cowell J. K. Application of intragenic DNA probes in prenatal screening for retinoblastoma gene carriers in the United Kingdom. Arch Dis Child. 1990 Jul;65(7 Spec No):651–656. doi: 10.1136/adc.65.7_spec_no.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scheffer H., te Meerman G. J., Kruize Y. C., van den Berg A. H., Penninga D. P., Tan K. E., der Kinderen D. J., Buys C. H. Linkage analysis of families with hereditary retinoblastoma: nonpenetrance of mutation, revealed by combined use of markers within and flanking the RB1 gene. Am J Hum Genet. 1989 Aug;45(2):252–260. [PMC free article] [PubMed] [Google Scholar]
  17. Sparkes R. S., Murphree A. L., Lingua R. W., Sparkes M. C., Field L. L., Funderburk S. J., Benedict W. F. Gene for hereditary retinoblastoma assigned to human chromosome 13 by linkage to esterase D. Science. 1983 Feb 25;219(4587):971–973. doi: 10.1126/science.6823558. [DOI] [PubMed] [Google Scholar]
  18. Vogel F. Genetics of retinoblastoma. Hum Genet. 1979 Nov 1;52(1):1–54. doi: 10.1007/BF00284597. [DOI] [PubMed] [Google Scholar]
  19. Wiggs J., Nordenskjöld M., Yandell D., Rapaport J., Grondin V., Janson M., Werelius B., Petersen R., Craft A., Riedel K. Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene. N Engl J Med. 1988 Jan 21;318(3):151–157. doi: 10.1056/NEJM198801213180305. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES