ABSTRACT
Spontaneous and mitomycin C(MMC)-induced sister chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify whether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.
Subject(s)
Crossing Over, Genetic , Retinoblastoma/genetics , Sister Chromatid Exchange , Cells, Cultured , Child, Preschool , Chromatids/drug effects , Dose-Response Relationship, Drug , Female , Humans , Infant , Lymphocytes/ultrastructure , Male , Mitomycins/pharmacology , Skin/ultrastructure , Time FactorsABSTRACT
Segregation analysis was performed in 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 possibility 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.
Subject(s)
Probability , Retinoblastoma/genetics , Genes, Dominant , Genetic Carrier Screening , Homozygote , Humans , Mathematics , Pedigree , PhenotypeABSTRACT
An excess of cancer deaths was found in grandparents of 308 children with retinoblastoma. This excess was found in all types of retinoblastoma, unilateral and bilateral, sporadic and familial. We postulated that the excess could be the result of a factor of susceptibility to cancer, different from the retinoblastoma gene, which would increase the mutation rate in retinal and germ cells as well as in other tissues.
Subject(s)
Neoplasms/mortality , Retinoblastoma/genetics , Female , France , Gene Frequency , Humans , Male , Neoplasms/epidemiology , Vital StatisticsABSTRACT
To test Knudson's hypothesis that two successive mutations are involved in retinoblastoma, we studied the data on 899 cases. Some of the findings appeared to differ from those that might be expected if Knudson's hypothesis were correct. Certain criticisms of Knudson's methodology and model were suggested. Alternative explanations proposed were 1) the role of the sequence in which mutations occur, and 2) the possibility of three mutational events.
Subject(s)
Models, Biological , Neoplasms/etiology , Retinoblastoma/genetics , Adolescent , Age Factors , Child , Child, Preschool , Family Characteristics , Germ Cells , Humans , Infant , Infant, Newborn , Mathematics , Mutation , Neoplasms, Multiple PrimaryABSTRACT
Study of malformations of the hand makes possible the definition of three forms of progressive severity in the Poland syndrome, in which there is unilateral symbrachydactylie associated with homolateral aplasia of the pectoralis major. The three forms share the predominance of involvement of the 2nd, 3rd and 4th fingers. The existence of alterations in palmar creases and dermatoglyphia of the involved side alone confirms the absence of any lesion, even infra-clinical, of the other hand. Genetic study favours a pluri-factorial inheritance. Topographical data and the comparative study of vascularisation suggest the possibility of hypoplasia of the proximal portion of the sub-clavian at the origin of this malformative association.
Subject(s)
Hand Deformities, Congenital , Pectoralis Muscles/abnormalities , Abnormalities, Multiple/embryology , Abnormalities, Multiple/genetics , Adult , Child , Dermatoglyphics , Female , Humans , Male , PedigreeABSTRACT
The frequency of retinoblastoma was estimated in southwest France (Midi-Pyrénées) during the 1950-1969 period. Twenty-three cases were detected among 507 157 liveborns. After correcting for the probability of ascertainment of patient, the estimated frequency is 1 per 15 849 births. The proportion of unilateral cases is estimated 91 percent after correcting for the higher probability of ascertaining bilateral cases.
Subject(s)
Eye Neoplasms/epidemiology , France , Humans , Retrospective StudiesABSTRACT
A complete family investigation was made for 598 cases of retinoblastoma and details of any associated congenital malformations were recorded. Associated malformations were found in seven cases, four of which were cleft palate. There was a highly significant difference between the frequency of cleft palate in our cases with retinoblastoma and the frequency in the general population. This result supports the hypothesis that cases of retinoblastoma with associated congenital malformations are caused by germinal mutations.
