Frequency of somatic and germ-line mosaicism in retinoblastoma: Implications for genetic counseling
Frequency of somatic and germ-line mosaicism in retinoblastoma: Implications for genetic counseling
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DOI：
10.1086/301766
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发表时间：
1998-03-01
影响因子：
9.8
通讯作者：
Dryja, TP
中科院分区：
文献类型：
--
作者：
Sippel, KC;Fraioli, RE;Dryja, TP
虽然嵌合现象对遗传性疾病家族的遗传咨询具有重要意义，但关于嵌合现象发生率的信息仅适用于少数几种一般疾病。在这里，我们描述了一个评估的156个家庭与视网膜母细胞瘤的初始致癌突变的视网膜母细胞瘤基因已被确定在这些家庭中，在15个（类似于10%）家庭，Ne能够文件镶嵌的初始突变的视网膜母细胞瘤基因，无论是在先证者或先证者的父母之一。在这156个家庭中，嵌合体的真实发生率可能高于我们的研究结果;在我们确定的15个家庭之外的其他一些家庭中，嵌合体很可能但无法得到证实，因为无法获得关键家庭成员的体细胞或生殖系DNA。分析了两个嵌合体父亲的生殖系DNA：其中一个在精子和白细胞DNA中都检测到突变;另一个仅在精子DNA中检测到突变。我们的数据表明，镶嵌现象比通常认为的更常见，特别是在视网膜母细胞瘤等疾病中，其中很高比例的病例代表nem突变。嵌合体的可能性，应始终考虑在新确定的家庭与视网膜母细胞瘤的遗传咨询，如这里所示，生殖系DNA的通用测试可以提供有价值的信息，是不能通过分析体细胞（白细胞）DNA。
Although mosaicism can have important implications for genetic counseling of families with hereditary disorders, information regarding the incidence of mosaicism is available for only a few generic diseases. Here we describe an evaluation of 156 families with retinoblastoma; the initial oncogenic mutation in the retinoblastoma gene had been identified in these families, In 15 (similar to 10%) families, Ne were able to document mosaicism for the initial mutation in the retinoblastoma gene, either in the proband or in one of the proband's parents. The true incidence of mosaicism in this group of 156 families is probably higher than our findings indicate; in some additional families beyond the 15 we identified, mosaicism was likely but could not be proven, because somatic or germ-line DNA from key family members was unavailable. Germ-line DNA from Two mosaic fathers was analyzed: in one of these, the mutation was detected in both sperm and leukocyte DNA; in the other, the mutation was detected only in sperm DNA. Our data suggest that mosaicism is more common than is generally appreciated, especially In disorders such as retinoblastoma, in which a high proportion of cases represent nem mutations. The possibility of mosaicism should always be considered during the genetic counseling of newly identified families with retinoblastoma, As demonstrated here, generic tests of germ-line DNA can provide valuable information that is not available through analysis of somatic (leukocyte) DNA.