Munné S, Morrison L, Fung J, Márquez C, Weier U, Bahçe M, Sable D, Grundfeld L, Schoolcraft B, Scott R, Cohen J
Institute for Reproductive Medicine and Science, Saint Barnabas Medical Center, Livingston, New Jersey 07052, USA.
J Assist Reprod Genet. 1998 May;15(5):290-6. doi: 10.1023/a:1022544511198.
Preimplantation genetic diagnosis of translocations has seldom been attempted. Recently, a genetic test based on analyzing polar bodies at the methaphase stage, following fluorescent in situ hybridization with commercially available whole-chromosome painting DNA probes has been presented. Here we report the use of this method in seven couples in whom the female was a carrier of one of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases), 46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2), 46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;q11).
The original method was improved in two ways. First, centromeric probes for one or both chromosomes involved in the translocation were added to avoid misdiagnosis caused by possible confusion of first polar body monovalent chromosomes (with two chromatids each) with single chromatids. Second, for cases with terminal translocations where commercially available probes do not cover telomere sequences, a telomere probe labeling the translocated fragment was added.
A total of 26 abnormal, 18 balanced, and 22 normal eggs was detected. Nine normal and seven balanced embryos were transferred, resulting in eight (50%) implanting, of which one spontaneously aborted. To date, the remainder have produced karyotypically normal or balanced babies and ongoing pregnancies. The rate of spontaneous abortions after preimplantation genetic diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural cycles in the same patients (95%).
With the above improvements, the test can characterize any translocation of maternal origin and produce a high pregnancy rate and an apparently low frequency of spontaneous abortion.
植入前基因诊断易位情况的尝试很少。最近，有人提出了一种基因检测方法，该方法基于在中期阶段分析极体，随后使用市售的全染色体涂染DNA探针进行荧光原位杂交。在此，我们报告该方法在七对夫妇中的应用情况，其中女性是这些平衡易位之一的携带者：45,XX,der(13q;14q)(q10;q10)（2例）、46,XX,t(4;14)(p15.3;q24)、45,XX,der(14q;21q)(q10;q10)、46,XX,t(7;20)(q22;q11.2)、46,XX,t(9,11)(p24;q12)、46,XX,t(14;18)(q22;q11)以及46,XX,t(3;8)(q11;q11)。
原方法在两个方面得到改进。第一，添加了与易位涉及的一条或两条染色体对应的着丝粒探针，以避免因第一极体单价染色体（每条有两条染色单体）可能与单条染色单体混淆而导致的误诊。第二，对于末端易位且市售探针未覆盖端粒序列的情况，添加了标记易位片段的端粒探针。
共检测到26个异常卵子、18个平衡卵子和22个正常卵子。移植了9个正常胚胎和7个平衡胚胎，其中8个（50%）着床，其中1个自然流产。迄今为止，其余胚胎均生出了染色体核型正常或平衡的婴儿，还有正在进行的妊娠。与同一患者自然周期（95%）相比，植入前基因诊断后的自然流产率（12.5%）显著降低（P<0.001）。
通过上述改进，该检测能够鉴定任何母源易位情况，并产生高妊娠率以及明显较低的自然流产频率。
