Low penetrance of retinoblastoma for p.V654L mutation of the RB1 gene
Low penetrance of retinoblastoma for p.V654L mutation of the RB1 gene
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DOI：
10.1186/1471-2350-12-76
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发表时间：
2011-05-26
影响因子：
--
通讯作者：
Su, Yi-Ning
中科院分区：
文献类型：
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作者：
Hung, Chia-Cheng;Lin, Shin-Yu;Su, Yi-Ning
背景：视网膜母细胞瘤是由视网膜母细胞瘤基因（RB1）突变的复合杂合或纯合性引起的。在种系视网膜母细胞瘤中，RB1基因突变使个体在发育过程中易患癌症风险增加。这些突变分离为高外显率（90%）的常染色体显性性状。方法：采用高分辨率熔解法和DNA直接测序法对一个家族的30名成员进行RB1基因突变筛选。我们评估了台湾一个大家族RB1基因种系突变的表型和外显率。结果：该家族的分子分析和临床细节显示，11名家族成员的RB1基因外显子19的p. V654L突变与表型变异有关。表型变化从无症状到单侧肿瘤的存在。只有4人（2男2女）发展为单侧视网膜母细胞瘤，计算外显率为36%（4/11）。这四名视网膜母细胞瘤患者是在三岁前被诊断出来的。他们的亲属没有表现出不同的严重程度或双侧视网膜母细胞瘤。结论：该家族的病眼率为0.36，低于目前的估计。这表明RB1 p. V654L突变是一种典型的低外显率突变。
Background: Retinoblastoma is caused by compound heterozygosity or homozygosity of retinoblastoma gene (RB1) mutations. In germline retinoblastoma, mutations in the RB1 gene predispose individuals to increased cancer risks during development. These mutations segregate as autosomal dominant traits with high penetrance (90%).Methods: We screened 30 family members from one family using high resolution melting assay and DNA direct sequencing for mutations in the RB1 gene. We evaluate the phenotype and penetrance of germline mutations of the RB1 gene in a large Taiwanese family.Results: The molecular analysis and clinical details of this family showed phenotypic variability associated with the p. V654L mutation in exon 19 of the RB1 gene in 11 family members. The phenotype varied from asymptomatic to presence of a unilateral tumor. Only four individuals (2 males and 2 females) developed unilateral retinoblastoma, which resulted in calculated low penetrance of 36% (4/11). The four individuals with retinoblastoma were diagnosed before the age of three years. None of their relatives exhibited variable severity or bilateral retinoblastoma.Conclusions: The diseased-eye ratio for this family was 0.36, which is lower than current estimates. This suggests that the RB1 p. V654L mutation is a typical mutation associated with low penetrance.