Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.

Autor: Bonini KE; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Thomas-Wilson A; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Marathe PN; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Sebastin M; Division of Pediatric Genetic Medicine, Department of Pediatrics, Children's Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA., Odgis JA; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Di Biase M; Division of Pediatric Genetic Medicine, Department of Pediatrics, Children's Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA., Kelly NR; Division of Pediatric Genetic Medicine, Department of Pediatrics, Children's Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA., Ramos MA; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Institute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Insel BJ; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Scarimbolo L; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Rehman AU; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Guha S; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Okur V; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Abhyankar A; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Phadke S; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Nava C; Molecular Diagnostics, New York Genome Center, New York, New York, USA., Gallagher KM; Division of Pediatric Genetic Medicine, Department of Pediatrics, Children's Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA., Elkhoury L; Sema4, Stamford, Connecticut, USA., Edelmann L; Sema4, Stamford, Connecticut, USA., Zinberg RE; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Abul-Husn NS; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Diaz GA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Greally JM; Division of Pediatric Genetic Medicine, Department of Pediatrics, Children's Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA., Suckiel SA; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Horowitz CR; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Institute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Kenny EE; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Wasserstein M; Division of Pediatric Genetic Medicine, Department of Pediatrics, Children's Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, USA., Gelb BD; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Jobanputra V; Molecular Diagnostics, New York Genome Center, New York, New York, USA.; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2023 Aug; Vol. 104 (2), pp. 210-225. Date of Electronic Publication: 2023 Jun 19.
DOI: 10.1111/cge.14365
Abstrakt: Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: