Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing.

Abstract

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

• Authors: Can Liao, Ai-hua Yin, Chun-fang Peng, Fang Fu, Jie-xia Yang, Ru Li, Yang-yi Chen, Dong-hong Luo, Yong-ling Zhang, Yan-mei Ou, Jian Li, Jing Wu, Ming-qin Mai, Rui Hou, Frances Wu, Hongrong Luo, Dong-zhi Li, Hai-liang Liu, Xiao-zhuang Zhang, Kang Zhang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 20 Pg. 7415-20 (May 20 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 24799683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Aneuploidy
• Chromosome Disorders (diagnosis)
• Chromosomes, Human, Pair 13
• Chromosomes, Human, Pair 18
• Cost-Benefit Analysis
• Down Syndrome (diagnosis)
• Female
• High-Throughput Nucleotide Sequencing (instrumentation, methods)
• Humans
• Karyotyping
• Male
• Pregnancy
• Prenatal Diagnosis (methods)
• Prospective Studies
• Retrospective Studies
• Semiconductors
• Sensitivity and Specificity
• Trisomy (diagnosis)
• Trisomy 13 Syndrome
• Trisomy 18 Syndrome