视网膜母细胞瘤低外显率一家系基因研究  

Analysis of gene mutation in a Chinese family with low penetrance retinoblastoma

作　　者：薛康[1] 吴继红[1] 任慧[1] 张锐[1] 钱江[1] 

机构地区：[1]复旦大学附属眼耳鼻喉科医院眼科,上海200031

出　　处：《中华眼底病杂志》2015年第6期553-555,共3页Chinese Journal of Ocular Fundus Diseases

基　　金：国家自然科学基金青年项目（81100656/H1203）;上海市卫生局青年基金（20144Y0263）

摘　　要：目的明确一国人低外显率视网膜母细胞瘤（RB）家系基因突变位点。方法对一个3代9人的汉族RB家系成员进行临床观察。采集家系中6人外周静脉血并提取基因组DNA。运用外显子结合目标区域捕获测序芯片进行检测；对候选致病性突变位点运用Sanger验证，确定致病性突变位点。结果家系9人中，先证者（Ⅲ2）为双眼RB，Ⅲ1为单眼RB；Ⅲ3为双眼RB，已死亡。除先证者外，Ⅲ1左眼及其他所有受试者眼底检查结果正常。基因检测结果显示，RB患儿及2名携带者（Ⅱ2、Ⅱ3）Rb1基因检出一个错义突变c．1981C〉T（P．Arg661Trp）；2名正常者（Ⅱ1、Ⅱ4）未发现该突变。推测该家系RB外显率为50％。结论国人-RB低外显率家系中发现Rb1基因错义突变c．1981C〉T；RB外显率为50％。Objective To identify the pathogenic mutation in a three generation Chinese family with low penetranee retinoblastoma （RB）. Methods 8 from 9 family members received complete ophthalmic examinations. DNA was extracted from 6 family members. Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations. Sanger sequencing were used to confirm the disease-causing mutation. Results Among 9 family members, the proband （Ⅲ 2） was bilateral RB, Ⅲ 1 was unilateral RB, Ⅲ 3 was dead for bilateral RB. Normal fundus were observed in the left eye of Ⅲ 1 and the eyes of other family members except the proband. Sequence analysis of RB1 gene revealed a missense mutation c. 1981C〉T （p. Arg661Trp） in the proband and two carriers （ Ⅱ 2, Ⅱ3）, but not in the two normal subjects （ Ⅱ 1,Ⅲ 4）. We suspect that the RB penetrance in the family was 50 %. Conclusions There is a missense mutation c. 1981C〉T in a Chinese family with low penetrance RB. The RB penetrance is 50%.

关 键 词：视网膜母细胞瘤 基因 肿瘤 外显率 高通量核苷酸序列分析 

分 类 号：R739.7[医药卫生—肿瘤]