Diagnostic Utility of Whole Genome Sequencing After Negative Karyotyping/Chromosomal Microarray in Infants Born With Multiple Congenital Anomalies.

Autor:	Yang M; Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.; Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Kim JA; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.; Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea., Jo HS; Department of Pediatrics, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea., Park JH; Clinical Genomics Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Ahn SY; Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.; Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Sung SI; Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.; Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Park WS; Department of Pediatrics, CHA Gangnam Medical Center, CHA University, Seoul, Korea., Cho HW; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea., Kim JM; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea., Park MH; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea., Park HY; National Institute of Health, Cheongju, Korea., Jang JH; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jahyun.jang@samsung.com., Chang YS; Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.; Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea. yschang@skku.edu.
Jazyk:	angličtina
Zdroj:	Journal of Korean medical science [J Korean Med Sci] 2024 Sep 23; Vol. 39 (36), pp. e250. Date of Electronic Publication: 2024 Sep 23.
DOI:	10.3346/jkms.2024.39.e250
Abstrakt:	Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. Conclusion: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS. Competing Interests: The authors have no potential conflicts of interest to disclose. (© 2024 The Korean Academy of Medical Sciences.)
Databáze:	MEDLINE
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