Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Prenat Diagn. 2012 Apr;32(4):362-70. doi: 10.1002/pd.2948.
We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome 250K single-nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies.
Upon the detection of structural fetal anomalies, parents were offered a choice between QF-PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR and routine karyotyping (QF/karyo).
Two hundred twenty fetal samples were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153 (23%), an abnormal QF-PCR result was found. The remaining samples were analyzed by array, which revealed clinically relevant aberrations, including two known microdeletions, in 5/118 cases. Inherited copy number variants were detected in 11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118 and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was requested: 23/67 (34%) were abnormal with QF-PCR, and in 3/67, an abnormal karyotype was found.
Even though QF/array does not reveal a high percentage of submicroscopic aberrations in fetuses with unselected structural anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at high resolution, without additional tests needed and with a low chance on findings not related to the ultrasound anomalies.
我们评估了新策略的临床和实验室方面，该策略提供定量荧光（QF）-PCR 检测，随后进行非靶向全基因组 250K 单核苷酸多态性微阵列分析，而不是常规核型分析，用于有结构异常的胎儿的产前诊断。
在检测到胎儿有结构异常后，父母可以在 QF-PCR 和 250K 单核苷酸多态性微阵列分析（QF/array）或 QF-PCR 和常规核型分析（QF/karyo）之间进行选择。
共纳入 220 个胎儿样本。在 220 例中有 153 例（70%）要求进行 QF/array 分析。在 35 例中有 153 例（23%）发现异常 QF-PCR 结果。其余样本进行了 array 分析，在 118 例中有 5 例发现了临床相关的畸变，包括两个已知的微缺失。在 118 例胎儿中有 11 例检测到遗传性拷贝数变异，3 例拷贝数变异具有不确定的临床意义，2 例为纯合片段。在 220 例中有 67 例（30%）要求进行 QF/karyo：23 例（34%）的 QF-PCR 异常，3 例中发现了异常核型。
即使 QF/array 在未选择有结构异常的胎儿中并未发现大量亚微观畸变，但它比 QF/karyo 更受欢迎，因为它提供了高分辨率的全基因组扫描，无需额外的测试，且发现与超声异常无关的结果的可能性较低。
