Prenatal Genetic Diagnosis of Fetal Cystic Hygroma: A Retrospective Single-Center Study from China.

IF 1.7 4区 生物学 Q4 CELL BIOLOGY
Yulin Zhou, Xingxiu Lu, Yanhong Zhang, Yunsheng Ge, Yasong Xu, Lili Wu, Yu Jiang
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引用次数: 0

Abstract

Fetal cystic hygroma (CH) is associated with poor prognosis and chromosomal anomalies. Recent studies have suggested that the genetic background of affected fetuses is essential for predicting pregnancy outcomes. However, the detection performance of different genetic approaches for the etiological diagnosis of fetal CH remains unclear. In this study, we aimed to compare the diagnostic efficiency of karyotyping and chromosomal microarray analysis (CMA) in a local fetal CH cohort, and tried to propose an optimized testing strategy that may help improve the cost-effectiveness of disease management. We reviewed all pregnancies that underwent invasive prenatal diagnosis between January 2017 and September 2021 at one of the largest prenatal diagnostic centers in Southeast China. We collected cases identified by the presence of fetal CH. Prenatal phenotypes and laboratory records of these patients were audited, collated, and analyzed. The detection rates of karyotyping and CMA were compared, and the concordance rate of these two methods was calculated. A total of 157 fetal CH cases were screened from 6,059 patients who underwent prenatal diagnosis. Diagnostic genetic variants were identified in 44.6% (70/157) of the cases. Karyotyping, CMA, and whole-exome sequencing (WES) identified pathogenic genetic variants in 63, 68, and 1 case, respectively. The Cohen's κ coefficient between karyotyping and CMA was 0.96, with a concordance of 98.0%. Of the 18 cases in which cryptic copy number variants <5 Mb were detected by CMA, 17 were interpreted as variants of uncertain significance, and the remaining cases were interpreted as pathogenic. Trio exome sequencing revealed a pathogenic homozygous splice site mutation in the PIGN gene in a case undiagnosed by CMA and karyotyping. Our study demonstrated that chromosomal aneuploidy abnormalities are the main genetic cause of fetal CH. Based on this, we recommend karyotyping combined with rapid aneuploidy detection as a first-tier approach for the genetic diagnosis of fetal CH. WES and CMA could improve the diagnostic yield when routine genetic tests fail to determine the cause of fetal CH.

胎儿囊性水肿的产前遗传学诊断:一项来自中国的回顾性单中心研究。
胎儿囊性水肿(CH)与预后不良和染色体异常有关。最近的研究表明,患病胎儿的遗传背景对预测妊娠结局至关重要。然而,不同的遗传方法对胎儿CH病因诊断的检测性能仍不清楚。在本研究中,我们旨在比较核型和染色体微阵列分析(CMA)在本地胎儿CH队列中的诊断效率,并试图提出一种优化的检测策略,以帮助提高疾病管理的成本效益。我们回顾了2017年1月至2021年9月在中国东南部最大的产前诊断中心之一接受有创产前诊断的所有孕妇。我们收集了由胎儿CH存在确定的病例。对这些患者的产前表型和实验室记录进行了审核、整理和分析。比较两种方法的检出率,并计算两种方法的符合率。从6,059例接受产前诊断的患者中共筛选157例胎儿CH病例。诊断性遗传变异占44.6%(70/157)。核型、CMA和全外显子组测序(WES)分别鉴定出63例、68例和1例致病性遗传变异。核型与CMA之间的Cohen’s κ系数为0.96,一致性为98.0%。其中18例隐式拷贝数变异
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来源期刊
Cytogenetic and Genome Research
Cytogenetic and Genome Research 生物-细胞生物学
CiteScore
3.10
自引率
5.90%
发文量
25
审稿时长
1 months
期刊介绍: During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.
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