Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma
Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma
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DOI：
10.1086/345651
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发表时间：
2003-02-01
影响因子：
9.8
通讯作者：
Gallie, B
中科院分区：
文献类型：
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作者：
Richter, S;Vandezande, K;Gallie, B
RB 1突变的及时分子诊断可以使视网膜母细胞瘤患者获得更早的治疗，更低的风险和更好的健康结果;使家庭能够做出明智的计划生育决定;并且比传统的监测成本更低。然而，复杂性阻碍了分子诊断的临床实施。大多数RB 1突变是独特的，分布在整个RB 1基因中，没有真实的热点。我们设计了一个敏感和有效的策略，以确定RB 1突变，结合定量多重聚合酶链反应（QM-PCR），双外显子测序，启动子靶向甲基化敏感的PCR。通过随机动态规划优化测试顺序和开发针对四个复发性点突变的等位基因特异性PCR，将估计周转时间缩短至
Timely molecular diagnosis of RB1 mutations enables earlier treatment, lower risk, and better health outcomes for patients with retinoblastoma; empowers families to make informed family-planning decisions; and costs less than conventional surveillance. However, complexity has hindered clinical implementation of molecular diagnosis. The majority of RB1 mutations are unique and distributed throughout the RB1 gene, with no real hot spots. We devised a sensitive and efficient strategy to identify RB1 mutations that combines quantitative multiplex polymerase chain reaction (QM-PCR), double-exon sequencing, and promoter-targeted methylation-sensitive PCR. Optimization of test order by stochastic dynamic programming and the development of allele-specific PCR for four recurrent point mutations decreased the estimated turnaround time to