Journal
GENETICS IN MEDICINE
Volume 18, Issue 9, Pages 940-948Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/gim.2015.199
Keywords
molecular karyotyping; next-generation sequencing; pathogenic copy-number variants
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Funding
- National Basic Research Program of China [2012CB944600]
- Shenzhen Municipal Commission for Development and Reform and Key Laboratory Project in Shenzhen [CXB200903110066A, CXB201108250096A]
- Medical Leading Talent and Innovation Team Project of Jiangsu Province [LJ201109]
- Key Technology R&D Program of Jiangsu Province [BL2012039, F201314]
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Purpose: Chromosomal microarray analysis is the gold standard for copy-number variant (CNV) detection in prenatal and postnatal diagnosis. We aimed to determine whether next-generation sequencing (NGS) technology could be an alternative method for CNV detection in routine clinical application; Methods: Genome-wide CNV analysis (>50kb) was performed On a multicenter group of 570 patients using a low-coverage whole-genome sequencing pipeline. These samples were referred for chromosomal analysis; CNVs (i.e., pathogenic CNVs, pCNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. Results: Overall, a total of 198 abortuses, 37 stillbirths, 149 prenatal, and 186 postnatal samples were tested. Our approach yielded results in 549 samples (96.3%). In addition to 119 subjects with aneuploidies, 103 pCNVs (74 losses and 29 gains) were identified in 82 samples, giving diagnostic yields of 53.2% (95% confidence interval: 45.8, 60.5), 14.7% (5.0, 31.1), 28.5% (21.1, 36.6), and 30.1% (23.6, 37.3) in each group, respectively. Mosaicism was observed at a level as low as 25%. Conclusions: Patients with chromosomal diseases or microdeletion/microduplication syndromes were diagnosed using a high-resolution genome-wide method. Our study revealed the potential of NGS to facilitate genetic diagnoses that were not evident in the prenatal and postnatal groups.
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