Department of Molecular and Human Genetics, Baylor College of Medicine, 6621 Fannin Street CC 1560, Houston, TX 77030, USA.
Obstet Gynecol Clin North Am. 2010 Mar;37(1):71-85, Table of Contents. doi: 10.1016/j.ogc.2010.02.001.
Current prenatal cytogenetic diagnosis uses mostly G-banded karyotyping of fetal cells from chorionic villi or amniotic fluid cultures, which readily detects any aneuploidy and larger structural genomic rearrangements that are more than 4 to 5 megabases in size. Fluorescence in situ hybridization (FISH) is also used for rapid detection of the common aneuploidies seen in liveborns. If there is prior knowledge that increases risk for a specific deletion or duplication syndrome, FISH with a probe specific for the region in question is done. Over the past decade, array-based comparative genomic hybridization (aCGH) has been developed, which can survey the entire genome for submicroscopic microdeletions and microduplications, in addition to all unbalanced chromosomal abnormalities that are also detected by karyotype. aCGH in essence interrogates the genome with thousands of probes fixed on a slide in a single assay, and has already revolutionized cytogenetic diagnosis in the pediatric population. aCGH is being used increasingly for prenatal diagnosis where it is also beginning to make a significant impact. The authors review here principles of aCGH, its benefits for prenatal diagnosis and associated challenges, primarily the inability to detect balanced chromosomal abnormalities and a small risk for discovery of chromosomal abnormalities of uncertain clinical significance. The superior diagnostic power of aCGH far outweighs these concerns. Furthermore, such issues can be addressed during pre- and posttest counseling, and their impact will further diminish as the technology continues to develop and experience with its prenatal diagnostic use grows.
目前的产前细胞遗传学诊断主要使用绒毛膜绒毛或羊水培养物中的胎儿细胞进行 G 带核型分析，这种方法可以轻易地检测到任何非整倍体和大于 4 到 5 兆碱基的较大结构基因组重排。荧光原位杂交（FISH）也用于快速检测在活产儿中常见的非整倍体。如果事先知道存在特定的缺失或重复综合征的风险，则可以进行针对特定区域的 FISH 探针检测。在过去的十年中，已经开发出基于阵列的比较基因组杂交（aCGH），除了可以通过核型检测到的所有不平衡染色体异常外，该方法还可以用于检测亚微观微缺失和微重复。aCGH 本质上是在单次检测中使用数千个固定在载玻片上的探针来检测整个基因组，并已经彻底改变了儿科人群的细胞遗传学诊断。aCGH 越来越多地用于产前诊断，并且也开始产生重大影响。作者在这里回顾了 aCGH 的原理、其在产前诊断中的益处和相关挑战，主要是无法检测到平衡的染色体异常以及发现具有不确定临床意义的染色体异常的风险较小。aCGH 的卓越诊断能力远远超过了这些担忧。此外，在测试前和测试后咨询期间可以解决这些问题，随着技术的不断发展以及对其产前诊断应用经验的不断增加，这些问题的影响将进一步减小。
