New molecular methods in prenatal diagnosis of aneuploidy mosaicism

点击翻译按钮获取中文摘要

The occurrence of mosaicism has been imposing a serious challenge to the prenatal diagnosis of chromosome abnormalities. The objective of this study is to investigate the frequency of chromosome mosaicism in prenatal diagnosis of amniotic fluid cells and to assess the utility of new molecular methods in the detection of mosaicism. The study subjects were 1,102 cases of amniotic fluid cell cultures. We categorized the mosaicism into a level 1 where a chromosome abnormality is seen in a single cell, level 2 where the abnormality is confined to plural cells in a single culture flask, and level 3 where the abnormality is seen in more than 2 flasks. A total of 77 (7.0%) cases were associated with any mosacism : 5 cases had the level 3 mosaicism [2 cases of trisomy 21, each case of trisomy 18, +inv dup (15) and t (14 ; 15)], 10 cases the level 2 mosaicism, and 62 cases the level 1 mosaicism. We applied the fluorescence in situ hybridization (FISH) and primed in situ hybridization (PRINS) methods to the diagnosis of the true mosaicism in the level 3 cases. Both FISH to alphoid DNA probes for chromosomes 15,18 and 21 and PRINS with primers specific to alphoid DNAs for chromosomes 18 and 21 showed significantly more signals on interphase nuclei in those cases than in normal controls. Furthermore, study in artificially made mosaic trisomy 18 showed that the FISH method can even detect a 12.5% of mosaicism. The very high frequency of chromosome mosaicism in amniotic fluid cell cultures suggest that much care should be taken to avoid misdiagnosis. We believe that FISH and PRINS methods which can analyze a great number of interphase cells in a short time are particularly useful in confirming the diagnosis of the true mosaicism.