Huang Q, Dryja T P, Yandell D W
Department of Ophthalmology, The First Affiliated Hospital, West China University of Medical Sciences, Chengdu, Sichuan Province, 610041 P.R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1998 Jun 10;15(3):139-42.
To investigate the possible cause and molecular mechanism of low penetrance in hereditary retinoblastoma kindred.
The DNAs from tumor or blood of affected and unaffected individuals in hereditary retinoblastoma families showing low penetrance were screened by SSCP analysis and further characterized by direct DNA sequencing.
Eight from fifteen families showing low penetrance retinoblastoma were identified to have distinct Rb gene point mutations including Arg661-Trp661 in five families, aberrant splicing in two families and a G-T mutation at ATF binding site of Rb gene promoter in one family.
The distribution of cases with low penetrance of retinoblastoma is not completely random. The low penetrance in the families described here was associated with several distinct Rb gene point mutations which did not result in complete disruption of the gene product,and the reduced penetrance of retinoblastoma is probably the result of a residual function of these alleles in retinoblastoma precursor cells.
探讨遗传性视网膜母细胞瘤家系中低外显率的可能原因及分子机制。
对表现出低外显率的遗传性视网膜母细胞瘤家系中患病和未患病个体的肿瘤组织或血液中的DNA进行单链构象多态性分析筛选，并通过直接DNA测序进一步鉴定。
在15个表现出低外显率视网膜母细胞瘤的家系中，有8个被鉴定出具有不同的Rb基因点突变，其中5个家系为Arg661-Trp661突变，2个家系为异常剪接，1个家系为Rb基因启动子的ATF结合位点发生G-T突变。
视网膜母细胞瘤低外显率病例的分布并非完全随机。本文所述家系中的低外显率与几种不同的Rb基因点突变有关，这些突变并未导致基因产物的完全破坏，视网膜母细胞瘤外显率降低可能是这些等位基因在视网膜母细胞瘤前体细胞中具有残余功能的结果。
