Summary
Segregation analysis was performed on 211 nuclear families belonging to 166 pedigrees of hereditary retinoblastoma found in a number of series which have been gathered from the literature. Bilaterally affected carriers appear homogeneous. The segregation ratio in their offspring is 0.49, and the proportion of bilateral cases among affected offspring is 0.87. Both unilaterally affected and unaffected carriers appear heterogeneous. The very low segregation ratio (0.08) in the offspring of unilateral carriers who are not detected through an affected child, suggests the possiblity of two types of carriers, “high” and “low transmitters”. The proportions of “low transmitters” was estimated as 0.14 among all familial unilateral carriers and as 0.45 among all detected unaffected carriers. Unilateral and unaffected “high transmitters” give a significantly lower segregation ratio than bilaterally affected carriers.
On the one hand, the existence of these two different types of carriers provides arguments in support of the hypothesis of delayed mutation. On the other hand, the differences in penetrance among “high transmitters,” according to their phenotype, supports the hypothesis of host resistance. Under the two-mutation hypothesis, the possibility that the mutation rate is variable among individuals and partly genetically determined, is suggested.
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References
Auerbach C (1956) A possible case of delayed mutation in man. Ann Hum Genet 20:266–269
Bonaïti-Pellié C, Briard-Guillemot ML, Feingold J, Frézal J (1976) Mutation theory of carcinogenesis in retinoblastoma. J Natl Cancer Inst 57:269–276
Bonaïti C, Demenais F (1980) Diseases having two classes of severity: Estimations of the proportions of each manifestation by maximum likelihood. Biometrics 36:447–460
Briard-Guillemot ML, Bonaïti-Pellié C, Feingold J, Frézal J (1974) Etude génétique de rétinoblastome. Hum Genet 24:271–284
Ellsworth RM (1969) The practical management of retinoblastoma. Trans Am Ophthalmol Soc 67:462–534
Falls HF, Neel JV (1951) Genetics of retinoblastoma. Arch Ophthalmol 46:367–389
Herrmann J (1976) Delayed mutation as a cause of retinoblastoma: Application to genetic counseling. Birth Defects 12:79–90
Herrmann J (1977) Delayed mutation model: Carotid body tumors and retinoblastoma. In: Mulvihill JJ, Miller RW, Fraumeni JF (eds) Genetics of human cancer. Raven Press, New York, p 417
Hethcote HW, Knudson AG (1978) Model for the incidence of embryonal cancers: Application to retinoblastoma. Proc Natl Acad Sci USA 75:2453–2457
Knudson AG (1971) Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823
Knudson AG, Hethcote HW, Brown BW (1975) Mutation and childhood cancer: A probabilitic model for the incidence of retinoblastoma. Proc Natl Acad Sci USA 72:5116–5120
Macklin MT (1960) A study of retinoblastoma in Ohio. Am J Hum Genet 12:1–43
Matsunaga E, Ogyu H (1976) Retinoblastoma in Japan: Follow-up survey of sporadic cases. Jap J Ophthalmol 20:266–282
Matsunaga E (1978) Hereditary retinoblastoma: Delayed mutation or host resistance? Am J Hum Genet 30:406–424
Matsunaga E (1979) Hereditary retinoblastoma: Host resistance and age at onset. J Natl Cancer Inst 63:933–939
Matsunaga E, Ogyu H (1976) Retinoblastoma in Japan: Follow-up survey of sporadic cases. Jpn J Ophthalmol 20:266–282
Morton NE (1959) Genetic tests under incomplete ascertainment. Am J Hum Genet 11:1–16
Neel JV (1962) Mutations in the human population. In: Burdette WJ (ed) Methodology in human genetics. Holden Day, San Francisco, p 203
Schappert-Kimmijser J, Hemmes GD, Nijland R (1966) The heredity of retinoblastoma. Ophthalmologica 151:197–213
Sorsby A (1972) Bilateral retinoblastoma: a dominantly inherited affection. Br Med J 2:580–583
Tucker DP, Streinberg AG, Cogan DG (1957) Frequency of genetic transmission of sporadic retinoblastoma. Arch Ophthalmol 57: 532–535
Vogel F (1957) Neue Untersuchungen zur Genetik des Retinoblastoms (Glioma retinae). Z Menschl Vererb-Konstit-Lehre 34:205–236
Vogel F (1979) Genetics of retinoblastoma. Hum Genet 52:1–54
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Bonaïti-Pellié, C., Briard-Guillemot, M.L. Segregation analysis in hereditary retinoblastoma. Hum Genet 57, 411–419 (1981). https://doi.org/10.1007/BF00281695
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DOI: https://doi.org/10.1007/BF00281695