|Title||Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Yang, L, Wei, Z, Chen, X, Hu, L, Peng, X, Wang, J, Lu, C, Kong, Y, Dong, X, Ni, Q, Lu, Y, Wu, B, Wang, H, Meirelles, K, Tian, X, Zhang, J, Chang, F, Liu, L, Li, C, You, W, Cheng, G, Wang, L, Cao, Y, Chen, C, Fang, P, Tang, S, Zhou, W|
|Date Published||2022 Jan|
|Keywords||Alleles, China, Chromosome Mapping, DNA Copy Number Variations, Exome Sequencing, Female, Genetic Association Studies, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genetic Testing, Humans, INDEL Mutation, Intensive Care Units, Neonatal, Male, Polymorphism, Single Nucleotide, Whole Genome Sequencing|
Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.
|Alternate Journal||Clin Genet|
|Grant List||20Z11900600 / / Shanghai Municipal Science and Technology Major Project / |
2017SHZDZX01 / / Shanghai Municipal Science and Technology Major Project /
2018SHZDZX05 / / Shanghai Municipal Science and Technology Major Project /
Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China.
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