Clinical use of whole exome sequencing in children with developmental delay/intellectual disability
Background: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole...
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Elsevier
2024-09-01
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| Series: | Pediatrics and Neonatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957224000044 |
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| author | Yoon Hee Jo Soo Han Choi Hye Won Yoo Min Jung Kwak Kyung Hee Park Juhyun Kong Yun-Jin Lee Sang Ook Nam Bo Lyun Lee Woo Yeong Chung Seung Hwan Oh Young Mi Kim |
| author_facet | Yoon Hee Jo Soo Han Choi Hye Won Yoo Min Jung Kwak Kyung Hee Park Juhyun Kong Yun-Jin Lee Sang Ook Nam Bo Lyun Lee Woo Yeong Chung Seung Hwan Oh Young Mi Kim |
| author_sort | Yoon Hee Jo |
| collection | DOAJ |
| description | Background: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. Methods: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. Results: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. Conclusion: The diagnostic yield of WES was 48.8 %. We conclude that patients’ characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype. |
| format | Article |
| id | doaj-art-a4d1213e053b4a4dbc22bd284f03ba46 |
| institution | DOAJ |
| issn | 1875-9572 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj-art-a4d1213e053b4a4dbc22bd284f03ba462025-08-20T03:03:45ZengElsevierPediatrics and Neonatology1875-95722024-09-0165544545010.1016/j.pedneo.2023.05.015Clinical use of whole exome sequencing in children with developmental delay/intellectual disabilityYoon Hee Jo0Soo Han Choi1Hye Won Yoo2Min Jung Kwak3Kyung Hee Park4Juhyun Kong5Yun-Jin Lee6Sang Ook Nam7Bo Lyun Lee8Woo Yeong Chung9Seung Hwan Oh10Young Mi Kim11Department of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Republic of KoreaDepartment of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Republic of KoreaDepartment of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Republic of KoreaDepartment of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Republic of KoreaDepartment of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Republic of KoreaDepartment of Pediatrics, Pusan National University Children's Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Yangsan, Republic of KoreaDepartment of Pediatrics, Pusan National University Children's Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Yangsan, Republic of KoreaDepartment of Pediatrics, Pusan National University Children's Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Yangsan, Republic of KoreaDepartment of Pediatrics, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of KoreaDepartment of Pediatrics, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of KoreaDepartment of Laboratory Medicine, Pusan National University Yangsan Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Yangsan, Republic of KoreaDepartment of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, Republic of Korea; Corresponding author. Department of Pediatrics, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602, Republic of Korea.Background: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. Methods: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. Results: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. Conclusion: The diagnostic yield of WES was 48.8 %. We conclude that patients’ characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype.http://www.sciencedirect.com/science/article/pii/S1875957224000044Whole exome sequencingNext generation sequencingDevelopmental delayIntellectual disability |
| spellingShingle | Yoon Hee Jo Soo Han Choi Hye Won Yoo Min Jung Kwak Kyung Hee Park Juhyun Kong Yun-Jin Lee Sang Ook Nam Bo Lyun Lee Woo Yeong Chung Seung Hwan Oh Young Mi Kim Clinical use of whole exome sequencing in children with developmental delay/intellectual disability Pediatrics and Neonatology Whole exome sequencing Next generation sequencing Developmental delay Intellectual disability |
| title | Clinical use of whole exome sequencing in children with developmental delay/intellectual disability |
| title_full | Clinical use of whole exome sequencing in children with developmental delay/intellectual disability |
| title_fullStr | Clinical use of whole exome sequencing in children with developmental delay/intellectual disability |
| title_full_unstemmed | Clinical use of whole exome sequencing in children with developmental delay/intellectual disability |
| title_short | Clinical use of whole exome sequencing in children with developmental delay/intellectual disability |
| title_sort | clinical use of whole exome sequencing in children with developmental delay intellectual disability |
| topic | Whole exome sequencing Next generation sequencing Developmental delay Intellectual disability |
| url | http://www.sciencedirect.com/science/article/pii/S1875957224000044 |
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