Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders
Genetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. Howev...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.725259/full |
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| author | Xuejun Ouyang Yu Zhang Lijuan Zhang Jixuan Luo Ting Zhang Hui Hu Lin Liu Lieqiang Zhong Shaoying Zeng Pingyi Xu Zhenjiang Bai Lee-Jun Wong Jing Wang Jing Wang Chunli Wang Bin Wang Victor Wei Zhang Victor Wei Zhang |
| author_facet | Xuejun Ouyang Yu Zhang Lijuan Zhang Jixuan Luo Ting Zhang Hui Hu Lin Liu Lieqiang Zhong Shaoying Zeng Pingyi Xu Zhenjiang Bai Lee-Jun Wong Jing Wang Jing Wang Chunli Wang Bin Wang Victor Wei Zhang Victor Wei Zhang |
| author_sort | Xuejun Ouyang |
| collection | DOAJ |
| description | Genetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. However, mtDNA sequencing is not routinely available in rapid genetic diagnosis programs, which may fail to diagnose mtDNA mutation-associated diseases. Herein, we explored the clinical utility of rapid exome sequencing combined with mtDNA sequencing in critically ill pediatric patients with suspected genetic disorders. Rapid clinical exome sequencing (CES) was performed as a first-tier test in 40 critically ill pediatric patients (aged from 6 days to 15 years) with suspected genetic conditions. Blood samples were also collected from the parents for trio analysis. Twenty-six patients presented with neuromuscular abnormalities or other systemic abnormalities, suggestive of suspected mitochondrial diseases or the necessity for a differential diagnosis of other diseases, underwent rapid mtDNA sequencing concurrently. A diagnosis was made in 18 patients (45.0%, 18/40); three cases with de novo autosomal dominant variants, ten cases with homozygous or compound heterozygous variants, three cases with hemizygous variants inherited from mother, three cases with heterozygous variants inherited from either parent, and one case with a mtDNA mutation. The 18 patients were diagnosed with metabolic (n = 7), immunodeficiency (n = 4), cardiovascular (n = 2), neuromuscular (n = 2) disorders, and others. Genetic testing reports were generated with a median time of 5 days (range, 3–9 days). Thirteen patients that were diagnosed had an available medical treatment and resulted in a positive outcome. We propose that rapid exome sequencing combined with mitochondrial DNA sequencing should be available to patients with suspected mitochondrial diseases or undefined clinical features necessary for making a differential diagnosis of other diseases. |
| first_indexed | 2024-12-19T22:09:33Z |
| format | Article |
| id | doaj.art-54d458b4e02e4275b4a844c2ea17f170 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T22:09:33Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-54d458b4e02e4275b4a844c2ea17f1702022-12-21T20:03:56ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-08-011210.3389/fgene.2021.725259725259Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic DisordersXuejun Ouyang0Yu Zhang1Lijuan Zhang2Jixuan Luo3Ting Zhang4Hui Hu5Lin Liu6Lieqiang Zhong7Shaoying Zeng8Pingyi Xu9Zhenjiang Bai10Lee-Jun Wong11Jing Wang12Jing Wang13Chunli Wang14Bin Wang15Victor Wei Zhang16Victor Wei Zhang17Department of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Gastroenterology, Shanghai Children’s Hospital, Shanghai, ChinaDepartment of Gastroenterology, Shanghai Children’s Hospital, Shanghai, ChinaDepartment of Vasculocardiology, Guangdong Provincial People’s Hospital, Guangzhou, ChinaDepartment of Vasculocardiology, Guangdong Provincial People’s Hospital, Guangzhou, ChinaDepartment of Vasculocardiology, Guangdong Provincial People’s Hospital, Guangzhou, ChinaDepartment of Neurology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Critical Care Medicine, Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, United StatesDepartment of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, United StatesAmCare Genomics Lab, Guangzhou, ChinaAmCare Genomics Lab, Guangzhou, ChinaDepartment of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, United StatesAmCare Genomics Lab, Guangzhou, ChinaGenetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. However, mtDNA sequencing is not routinely available in rapid genetic diagnosis programs, which may fail to diagnose mtDNA mutation-associated diseases. Herein, we explored the clinical utility of rapid exome sequencing combined with mtDNA sequencing in critically ill pediatric patients with suspected genetic disorders. Rapid clinical exome sequencing (CES) was performed as a first-tier test in 40 critically ill pediatric patients (aged from 6 days to 15 years) with suspected genetic conditions. Blood samples were also collected from the parents for trio analysis. Twenty-six patients presented with neuromuscular abnormalities or other systemic abnormalities, suggestive of suspected mitochondrial diseases or the necessity for a differential diagnosis of other diseases, underwent rapid mtDNA sequencing concurrently. A diagnosis was made in 18 patients (45.0%, 18/40); three cases with de novo autosomal dominant variants, ten cases with homozygous or compound heterozygous variants, three cases with hemizygous variants inherited from mother, three cases with heterozygous variants inherited from either parent, and one case with a mtDNA mutation. The 18 patients were diagnosed with metabolic (n = 7), immunodeficiency (n = 4), cardiovascular (n = 2), neuromuscular (n = 2) disorders, and others. Genetic testing reports were generated with a median time of 5 days (range, 3–9 days). Thirteen patients that were diagnosed had an available medical treatment and resulted in a positive outcome. We propose that rapid exome sequencing combined with mitochondrial DNA sequencing should be available to patients with suspected mitochondrial diseases or undefined clinical features necessary for making a differential diagnosis of other diseases.https://www.frontiersin.org/articles/10.3389/fgene.2021.725259/fullrapid exome sequencingmitochondrial diseasesmtDNA sequencingpediatric patientsgenetic disorders |
| spellingShingle | Xuejun Ouyang Yu Zhang Lijuan Zhang Jixuan Luo Ting Zhang Hui Hu Lin Liu Lieqiang Zhong Shaoying Zeng Pingyi Xu Zhenjiang Bai Lee-Jun Wong Jing Wang Jing Wang Chunli Wang Bin Wang Victor Wei Zhang Victor Wei Zhang Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders Frontiers in Genetics rapid exome sequencing mitochondrial diseases mtDNA sequencing pediatric patients genetic disorders |
| title | Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders |
| title_full | Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders |
| title_fullStr | Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders |
| title_full_unstemmed | Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders |
| title_short | Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders |
| title_sort | clinical utility of rapid exome sequencing combined with mitochondrial dna sequencing in critically ill pediatric patients with suspected genetic disorders |
| topic | rapid exome sequencing mitochondrial diseases mtDNA sequencing pediatric patients genetic disorders |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.725259/full |
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