Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China.

TitleUse of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China.
Publication TypeJournal Article
Year of Publication2022
AuthorsYang, 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
JournalClin Genet
Volume101
Issue1
Pagination101-109
Date Published2022 Jan
ISSN1399-0004
Abstract

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.

DOI10.1111/cge.14075
Alternate JournalClin Genet
PubMed ID34671977
Grant List20Z11900600 / / Shanghai Municipal Science and Technology Major Project /
2017SHZDZX01 / / Shanghai Municipal Science and Technology Major Project /
2018SHZDZX05 / / Shanghai Municipal Science and Technology Major Project /