Macpherson J N, Nelson D L, Jacobs P A
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, Salisbury.
J Med Genet. 1992 Nov;29(11):802-6. doi: 10.1136/jmg.29.11.802.
In five of 40 fra(X) families reinvestigated using the new intragenic probe StB12.3, small amplifications of the DNA fragment appeared unexpectedly in addition to the mutations found in the probands. This suggests that enlargements of the FMR-1 gene detectable by Southern blotting using this probe must be present at an appreciable frequency in the general population. A proportion of these may be classifiable as 'premutations', or precursors of the much amplified, hypermethylated, and somatically unstable fragment associated with the fragile X syndrome, while others will merely represent stable polymorphisms in fragment length. Hence, accurate diagnosis of some fra(X) carriers will depend upon a more precise measurement of insert size than is currently provided by the newly available molecular probes.
在使用新的基因内探针StB12.3重新研究的40个脆性X综合征（fra(X)）家族中的5个家族中，除了在先证者中发现的突变外，DNA片段意外地出现了小的扩增。这表明，使用该探针通过Southern印迹法可检测到的FMR-1基因扩增在普通人群中必定以相当高的频率存在。其中一部分可能可归类为“前突变”，即与脆性X综合征相关的高度扩增、高度甲基化且体细胞不稳定片段的前体，而其他的可能仅仅代表片段长度的稳定多态性。因此，对一些fra(X)携带者的准确诊断将取决于对插入片段大小的更精确测量，这比目前新获得的分子探针所提供的测量更为精确。
