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伴有低外显率的Rb基因点突变及其特征和意义 |
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黄倩 Thaddeus P.Dryja David W.Yandell
【摘要】 目的 研究视网膜母细胞瘤患者(RB)低外显率的病因及其分子机理。方法 收集RB先证者及其家庭成员的RB肿瘤与外周血，通过SSCP分析和DNA序列测定检测Rb基因点突变，结合家系调查分析突变的特征及其与RB表型变化的关系。 结果 15个低外显率的RB家系中部份家系存在特殊类型的Rb基因点突变，其中5个家系有Arg661→Trp661突变，2个家系显示mRNA拼接位点异常，1个家系Rb基因启动子转录调控因子ATF结合位点改变。 结论 RB低外显率并非完全随机发生的，与Rb基因突变的位置和性质有密切关系。
【关键词】 视网膜母细胞瘤 Rb基因 点突变 低外显率
DISTINCT Rb GENE POINT MUTATIONS IN FAMILIES SHOWING LOW PENETRANCE OF HEREDITARY RETINOBLASTOMA Huang Qian*, Thaddeus P.Dryja, David W.Yandell.*Department of Ophthalmology, The First Affiliated Hospital, West China University of Medical Sciences, Chengdu 610041 P.R.China
【Abstract】 Objective To investigate the possible cause and molecular mechanism of low penetrance in hereditary retinoblastoma kindred. Methods 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. Results 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. Conclusion 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.
【Key words】 Retinoblastoma Rb gene Point mutation Low penetrance
大约10%～15%的视网膜母细胞瘤患者(retino-
blastoma，RB)有家族发病史［1］，临床表现为双眼肿瘤，并以常染色体显性遗传特征而传递，遗传了致病基因的个体又将发生双眼RB。然而，家系调查及突变基因分析发现某些遗传性RB家系中有的个体尽管存在Rb基因突变却不发生RB或仅单眼发病，此现象统称低外显率［2，3］。我们在对大宗RB病例R[1] [2] 下一页
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