Journal Article

Preliminary study of noninvasive prenatal screening for 22q11.2 deletion/duplication syndrome using multiplex dPCR assay

Zhou, Yan, Wang, Wei, Yu, Bin, Zhang, Bin, Zhou, Wenbo, Zhou, Linna, Wang, Xinyue, Wang, Jing

2023

Overview

Objective This study aimed to establish a cell-free fetal DNA (cffDNA) assay using multiplex digital PCR (dPCR) for identifying fetuses at increased risk of 22q11.2 deletion/duplication syndrome. Methods Six detection sites and their corresponding probes were designed for the 22q11.2 recurrent region. A dPCR assay for the noninvasive screening of 22q11.2 deletion/duplication syndrome was established. A total of 130 plasma samples from pregnant women (including 15 samples with fetal 22q11.2 deletion/duplication syndrome) were blindly tested for evaluating the sensitivity and specificity of the established assay. Results DNA with different sizes of 22q11.2 deletion/duplication was detected via dPCR, indicating that the designed probes and detection sites were reasonable and effective. In the retrospective clinical samples, 11 out of 15 samples of pregnant women with 22q11.2 deletion/duplication were detected during the cffDNA assay, and accurate regional localization was achieved. Among the 115 normal samples, 111 were confirmed to be normal. Receiver operating characteristic curves were used for assessing the cut-off values and AUC for these samples. The sensitivity, specificity, and positive as well as negative predictive values were 73.3%, 96.5%, 73.3%, and 96.5%, respectively. Conclusion The cffDNA assay based on dPCR technology for the noninvasive detection of 22q11.2 recurrent copy number variants in fetuses detected most affected cases, including smaller but relatively common nested deletions, with a low false-positive rate. It is a potential, efficient and simple method for the noninvasive screening of 22q11.2 deletion/duplication syndrome.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 22q11.2 deletion/duplication syndrome / Achondroplasia / Amniocentesis / Amniotic fluid / Cardiovascular disease / Childrens health / Chromosomes / Congenital diseases / Copy number / Diagnosis / Digital PCR (dPCR) / DNA probes / Fetuses / Genes / Genetic counseling / Gestational age / Human chromosome abnormalities / Human Genetics / Localization / Maternal & child health / Medical genetics / Medical research / Medical screening / Medicine / Medicine & Public Health / Medicine, Experimental / Methods / Noninvasive prenatal screening / Pharmacology/Toxicology / Plasma / Polymerase chain reaction / Pregnancy / Pregnant women / Prenatal diagnosis / Rare diseases / Risk factors / Sensitivity analysis / Software / Ultrasonic imaging / Womens health