Vogel F
Hum Genet. 1979 Nov 1;52(1):1-54. doi: 10.1007/BF00284597.
The genetic basis of retinoblastoma is reviewed and the following conclusions are drawn: 1) The mode of inheritance of the hereditary variety of retinoblastoma (R) is autosomal dominant with about 90% penetrance. 2) About 68% of inherited cases are bilateral, and about 32%, unilateral. There is an intrafamilial correlation between penetrance as measured by segregation ratio and expressivity as measured by the fraction of bilaterally affected patients. 3) The vast majority of all R patients are sporadic cases, i.e., they are the only affected members of otherwise unaffected families. The porportion of bilateral cases is much lower among sporadic than among hereditary cases. 4) All bilaterally affected patients with sporadic R and patients with unilateral sporadic R with more than one primary tumor have to be regarded as germ cell mutants; they will transmit the gene to 50% of their offspring. Only 10%-12% of unilateral sporadic cases are germ cell mutants; 88%-90% are nonhereditary; in these cases the tumor is probably caused by a somatic mutation. 5) In a minority of cases, deletion of the chromosome segment 13q14(=intersitital deletion of the long arm of chromosome 13) has been observed. In addition to R, the patients show a variable degree of general or mental retardation; often there are few external indications of a chromosome aberration. Other chromosome studies suggest anomalies of chromosome 13 in tumor tissue even in cases not showing an anomaly of this chromosome in blood cultures, and possibly a slightly increased chromosome instability. 6) Patients with bilateral, and possibly in general with hereditary, R run an increased risk of becoming affected with other tumor diseases, such as osseous sarcomas, in later life. 7) Knudson's hypothesis of two mutational steps leading to both the hereditary and the nonhereditary variants of R is discussed critically, and the alternative possibility is suggested that in the nonhereditary variant a single mutational step--possibly a small chromosome aberration--could be enough to produce a tumor. 8) Evidence indicating a possible viral origin of R is cited, and animal experiments are mentioned in which R-like tumors have successfully been produced by local DNA virus inoculation. 9) As a consequence of improved survival and reproduction of R patients, an increased in the incidence of R and in the proportion of bilateral cases among all R patients must be anticipated. 10) Detailed rules for genetic counseling in families affected by R are given.
本文综述了视网膜母细胞瘤的遗传基础，并得出以下结论：1）遗传性视网膜母细胞瘤（R）的遗传方式为常染色体显性遗传，外显率约为90%。2）约68%的遗传病例为双侧性，约32%为单侧性。以分离率衡量的外显率与以双侧受累患者比例衡量的表现度之间存在家族内相关性。3）所有视网膜母细胞瘤患者中的绝大多数为散发病例，即他们是原本未受影响家庭中唯一患病的成员。散发病例中双侧病例的比例远低于遗传病例。4）所有双侧受累的散发性视网膜母细胞瘤患者以及有多个原发肿瘤的单侧散发性视网膜母细胞瘤患者都必须被视为生殖细胞突变体；他们将把该基因传给50%的后代。只有10%-12%的单侧散发病例是生殖细胞突变体；88%-90%是非遗传性的；在这些病例中，肿瘤可能是由体细胞突变引起的。5）在少数病例中，观察到染色体13q14片段缺失（即13号染色体长臂的中间缺失）。除视网膜母细胞瘤外，患者还表现出不同程度的智力迟钝；通常几乎没有染色体畸变的外部迹象。其他染色体研究表明，即使在血液培养中未显示该染色体异常的病例中，肿瘤组织中也存在13号染色体异常，并且可能染色体不稳定性略有增加。6）双侧性视网膜母细胞瘤患者，可能一般遗传性视网膜母细胞瘤患者，在晚年患其他肿瘤疾病如骨肉瘤的风险增加。7）对克努森关于导致视网膜母细胞瘤遗传型和非遗传型的两个突变步骤的假说进行了批判性讨论，并提出了另一种可能性，即在非遗传型中，单个突变步骤——可能是一个小的染色体畸变——可能足以产生肿瘤。8）引用了表明视网膜母细胞瘤可能起源于病毒的证据，并提及了通过局部接种DNA病毒成功产生类似视网膜母细胞瘤肿瘤的动物实验。9）由于视网膜母细胞瘤患者存活率和繁殖率的提高，可以预期视网膜母细胞瘤的发病率以及所有视网膜母细胞瘤患者中双侧病例的比例将会增加。10）给出了受视网膜母细胞瘤影响家庭的遗传咨询详细规则。
