Turan Sifa, Asoglu Mehmet Resit, Gabbay-Benziv Rinat, Doyle Lauren, Harman Christopher, Turan Ozhan M
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, United States.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, United States.
Eur J Obstet Gynecol Reprod Biol. 2018 Feb;221:172-176. doi: 10.1016/j.ejogrb.2017.12.019. Epub 2017 Dec 12.
The purpose of this study was to calculate the yield rates of CMA in fetuses diagnosed with various CHDs in a tertiary center.
This cohort study collected prenatal genetic test results of 145 fetuses diagnosed with CHD. All 145 cases underwent Conventional karyotype (CK), followed by CMA in cases of negative CK result. "Detection rate" of genetic abnormalities was calculated as the percentage of cases with genetic abnormalities identified. The rate of genetic abnormalities detected by CK was first calculated, and then the cumulative detection rate was calculated in the study population. "Yield rate of CMA" was determined by subtracting the cumulative detection rate from the detection rate of CK. The cumulative detection rate was assumed to represent the detection rate of CMA since it is due to the fact that if CMA had been done for all patients before CK, it would have diagnosed all the genetic abnormalities in the study population, and thus it was named as anticipated CMA.
Of the 145 CHD cases, 92 (63.4%) had isolated CHD and 53 (36.6%) had concomitant CHD and extracardiac anomaly (ECA). The detection rate of genetic abnormalities was 14% and 33.8% for CK and anticipated-CMA respectively (p < .001). The yield rate of CMA was 19.8% and 16.1% before and after the exclusion of cases with 22q.11.2 deletion/duplication, respectively. The detection rates of genetic abnormalities for isolated CHD, and concomitant CHD-ECA groups were 6.5% and 26.4% by CK, and 23.9% and 50.9% by anticipated-CMA, respectively (p < .01). The yield rate of CMA was 17.4% and 24.5% for isolated CHD and concomitant CHD-ECA cases, respectively.
CMA increases the diagnostic yield in fetuses with CHD, regardless of whether it is isolated or not. CMA should be the modality of choice when investigating the genetic origin of CHDs until whole exome or genome sequencing is implemented into routine clinical practice.
本研究旨在计算在一家三级医疗中心被诊断患有各种先天性心脏病（CHD）的胎儿中，染色体微阵列分析（CMA）的检出率。
这项队列研究收集了145例被诊断患有CHD的胎儿的产前基因检测结果。所有145例病例均接受了常规核型分析（CK），CK结果为阴性的病例随后进行CMA。基因异常的“检出率”计算为检测到基因异常的病例所占的百分比。首先计算CK检测到基因异常的比率，然后计算研究人群中的累积检出率。“CMA的检出率”通过从CK的检出率中减去累积检出率来确定。累积检出率被假定代表CMA的检出率，因为如果在CK之前对所有患者都进行CMA，它将诊断出研究人群中的所有基因异常，因此将其命名为预期CMA。
在145例CHD病例中，92例（63.4%）为孤立性CHD，53例（36.6%）伴有CHD和心外异常（ECA）。CK和预期CMA检测基因异常的比率分别为14%和33.8%（p<0.001）。在排除22q.11.2缺失/重复病例之前和之后，CMA的检出率分别为19.8%和16.1%。孤立性CHD组和伴有CHD-ECA组的基因异常检出率，CK分别为6.5%和26.4%，预期CMA分别为23.9%和50.9%（p<0.01）。孤立性CHD和伴有CHD-ECA病例的CMA检出率分别为17.4%和24.5%。
无论CHD是否为孤立性，CMA均可提高胎儿CHD的诊断率。在全外显子组或基因组测序应用于常规临床实践之前，CMA应作为研究CHD遗传起源的首选方法。
