Misun Yang, Jee Ah Kim, Heui Seung Jo, Jong-Ho Park, So Yoon Ahn, Se In Sung, Won Soon Park, Hye-Won Cho, Jeong-Min Kim, Mi-Hyun Park, Hyun-Young Park, Ja-Hyun Jang, Yun Sil Chang
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引用次数: 0
Abstract
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.
期刊介绍：
The Journal of Korean Medical Science (JKMS) is an international, peer-reviewed Open Access journal of medicine published weekly in English. The Journal’s publisher is the Korean Academy of Medical Sciences (KAMS), Korean Medical Association (KMA). JKMS aims to publish evidence-based, scientific research articles from various disciplines of the medical sciences. The Journal welcomes articles of general interest to medical researchers especially when they contain original information. Articles on the clinical evaluation of drugs and other therapies, epidemiologic studies of the general population, studies on pathogenic organisms and toxic materials, and the toxicities and adverse effects of therapeutics are welcome.
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