Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
J Med Genet. 2010 Sep;47(9):586-94. doi: 10.1136/jmg.2009.075853. Epub 2010 Jun 24.
The implementation of microarray analysis in prenatal diagnostics is a topic of discussion, as rare copy number variants with unknown/uncertain clinical consequences are likely to be found. The application of targeted microarrays limits such findings, but the potential disadvantage is that relevant, so far unknown, aberrations might be overlooked. Therefore, we explore the possibilities for the prenatal application of the genome-wide 250k single nucleotide polymorphism array platform.
Affymetrix 250k NspI single nucleotide polymorphism array analysis (Affymetrix, Inc., Santa Clara, California, USA) was performed on DNA from 38 prenatally karyotyped fetuses with ultrasound anomalies. Analyses were performed after termination of pregnancy, intrauterine fetal death or birth on DNA isolated from fetal or neonatal material.
Aberrations were detected in 17 of 38 fetuses, 6 of whom with a previously identified chromosomal abnormality and 11 with previously normal or balanced karyotypes. Of the latter, the detected aberration occurred de novo and was considered of clinical relevance in five cases (16%), inherited from a healthy parent in four cases (12%), and de novo yet with unclear clinical relevance in two cases (6%). The clinically relevant abnormalities either were novel copy number variants (n=3) or concerned a uniparental disomy (n=2).
In at least 16% of fetuses with ultrasound anomalies and a normal or balanced karyotype, causal (submicroscopic) aberrations were detected, illustrating the importance of the (careful) implementation of microarray analysis in prenatal diagnosis. The fact that the identified, clinically relevant, aberrations would have gone undetected with most targeted approaches underscores the added value of a genome-wide approach.
微阵列分析在产前诊断中的应用是一个讨论的话题，因为可能会发现具有未知/不确定临床后果的罕见拷贝数变异。靶向微阵列的应用限制了这些发现，但潜在的缺点是可能会忽略相关的、迄今为止未知的异常。因此，我们探索了在产前应用全基因组 250k 单核苷酸多态性阵列平台的可能性。
对 38 例经超声异常产前核型的胎儿的 DNA 进行 Affymetrix 250k NspI 单核苷酸多态性阵列分析（Affymetrix，Inc.，加利福尼亚州圣克拉拉）。在终止妊娠、宫内胎儿死亡或新生儿出生后，对从胎儿或新生儿材料中分离的 DNA 进行分析。
在 38 例胎儿中有 17 例检测到异常，其中 6 例有先前确定的染色体异常，11 例有先前正常或平衡的核型。在后者中，检测到的异常是从头发生的，在 5 例（16%）中被认为具有临床相关性，在 4 例（12%）中遗传自健康父母，在 2 例（6%）中是从头发生的，但临床相关性不清楚。具有临床相关性的异常要么是新的拷贝数变异（n=3），要么涉及单亲二体性（n=2）。
在至少 16%的超声异常且核型正常或平衡的胎儿中，检测到因果（亚微观）异常，这说明了在产前诊断中谨慎实施微阵列分析的重要性。如果采用大多数靶向方法，所确定的、具有临床相关性的异常将无法被检测到，这突显了全基因组方法的附加价值。
