Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan
Background: Unexplained developmental delay or intellectual disability (DD/ID) has an estimated prevalence of about 3%–5% in the general population of Taiwan. Array comparative genomic hybridization (array-CGH) is a high-resolution tool that can detect about 50 Kb chromosome aberrations. A previous...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-08-01
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| Series: | Pediatrics and Neonatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957218302092 |
| _version_ | 1811235642188759040 |
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| author | Chung-Lin Lee Chen-Hao Lee Chih-Kuang Chuang Huei-Ching Chiu Yen-Jiun Chen Chao-Ling Chou Peih-Shan Wu Chih-Ping Chen Hsiang-Yu Lin Shuan-Pei Lin |
| author_facet | Chung-Lin Lee Chen-Hao Lee Chih-Kuang Chuang Huei-Ching Chiu Yen-Jiun Chen Chao-Ling Chou Peih-Shan Wu Chih-Ping Chen Hsiang-Yu Lin Shuan-Pei Lin |
| author_sort | Chung-Lin Lee |
| collection | DOAJ |
| description | Background: Unexplained developmental delay or intellectual disability (DD/ID) has an estimated prevalence of about 3%–5% in the general population of Taiwan. Array comparative genomic hybridization (array-CGH) is a high-resolution tool that can detect about 50 Kb chromosome aberrations. A previous study has reported a detection rate of 10%–20% for this array.1 This study aimed to investigate and compare the diagnosis rate for DD/ID using array-CGH and conventional chromosome study in DD/ID patients in Taiwan. Methods: We enrolled 177 patients with DD/ID who underwent array-CGH examination at the MacKay Memory Hospital between June 2010 and September 2017. The copy number variants (CNV) were classified into the following three groups: pathogenic (potential pathologic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance, VOUS), according to the ACMG guideline.2 Results: Of the 177 enrolled patients, 100 (56.5%) were men and 77 (43.5%) were women. Ages ranged from 3 months to 50 years, with a median age of 5.2 years. Total 32.0% (32/100) male patients had pathogenic CNV, and 32.5% (25/77) female patients had pathogenic CNV. The ratio of pathogenic CNV in male and female patients was not significantly different (p = 0.379). The proportions of pathogenic CNV at <3 years, 3–6 years, 6–12 years, 12–18 years, and >18 years of age were 32.3% (31/96), 19.4% (6/31), 34.8% (8/23), 16.7% (2/12), and 66.7% (10/15), respectively. The overall diagnosed rate of DD/ID with pathogenic CNV was 27.7% (49/177) using array-CGH in this study. There were 105 patients with conventional karyotyping and array-CGH data at the same time. Nineteen (18.1%) patients had visible chromosomal abnormality. Total 32/105 (30.5%) patients could find at least one pathogenic CNVs. The array-CGH had a higher diagnosed rate than the conventional karyotyping in clinical application. Conclusions: Although array-CGH could not detect point mutation, balanced translocations, inversions, or low-level mosaicism, the diagnosis rate in clinical application was up to 46.3% and 2.5 times that of conventional karyotyping analysis (18.1%). This study demonstrated that array-CGH is a powerful diagnostic tool and should be the first genetic test instead of conventional karyotyping analysis for patients with unexplained DD/ID. Key Words: array-CGH, chromosomal microarray, developmental delay, intellectual disabilities, Taiwan |
| first_indexed | 2024-04-12T11:55:25Z |
| format | Article |
| id | doaj.art-f29b8a4d59384effb36b6700a9a7b897 |
| institution | Directory Open Access Journal |
| issn | 1875-9572 |
| language | English |
| last_indexed | 2024-04-12T11:55:25Z |
| publishDate | 2019-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj.art-f29b8a4d59384effb36b6700a9a7b8972022-12-22T03:34:02ZengElsevierPediatrics and Neonatology1875-95722019-08-01604453460Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in TaiwanChung-Lin Lee0Chen-Hao Lee1Chih-Kuang Chuang2Huei-Ching Chiu3Yen-Jiun Chen4Chao-Ling Chou5Peih-Shan Wu6Chih-Ping Chen7Hsiang-Yu Lin8Shuan-Pei Lin9Department of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanDepartment of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung City, TaiwanMedical Research, Mackay Memorial Hospital, Taipei, TaiwanDepartment of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanDepartment of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanDepartment of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanGene Biodesign Co. Ltd., Taipei, TaiwanMedical Research, Mackay Memorial Hospital, Taipei, Taiwan; Departments of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, TaiwanDepartment of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan; Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Corresponding author. Division of Genetics and Metabolism, Departments of Pediatrics and Medical Research, Mackay Memorial Hospital, No.92, Sec. 2, Chung-Shan North Road, Taipei 10449, Taiwan. Fax: +886 2 2543 3642 and +886 2 2543 3535 ext. 3080.Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan; Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; Corresponding author. Department of Pediatrics, Mackay Memorial Hospital, No.92, Sec. 2, Chung-Shan North Road, Taipei 10449, Taiwan. Fax: +886 2 2543 3642.Background: Unexplained developmental delay or intellectual disability (DD/ID) has an estimated prevalence of about 3%–5% in the general population of Taiwan. Array comparative genomic hybridization (array-CGH) is a high-resolution tool that can detect about 50 Kb chromosome aberrations. A previous study has reported a detection rate of 10%–20% for this array.1 This study aimed to investigate and compare the diagnosis rate for DD/ID using array-CGH and conventional chromosome study in DD/ID patients in Taiwan. Methods: We enrolled 177 patients with DD/ID who underwent array-CGH examination at the MacKay Memory Hospital between June 2010 and September 2017. The copy number variants (CNV) were classified into the following three groups: pathogenic (potential pathologic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance, VOUS), according to the ACMG guideline.2 Results: Of the 177 enrolled patients, 100 (56.5%) were men and 77 (43.5%) were women. Ages ranged from 3 months to 50 years, with a median age of 5.2 years. Total 32.0% (32/100) male patients had pathogenic CNV, and 32.5% (25/77) female patients had pathogenic CNV. The ratio of pathogenic CNV in male and female patients was not significantly different (p = 0.379). The proportions of pathogenic CNV at <3 years, 3–6 years, 6–12 years, 12–18 years, and >18 years of age were 32.3% (31/96), 19.4% (6/31), 34.8% (8/23), 16.7% (2/12), and 66.7% (10/15), respectively. The overall diagnosed rate of DD/ID with pathogenic CNV was 27.7% (49/177) using array-CGH in this study. There were 105 patients with conventional karyotyping and array-CGH data at the same time. Nineteen (18.1%) patients had visible chromosomal abnormality. Total 32/105 (30.5%) patients could find at least one pathogenic CNVs. The array-CGH had a higher diagnosed rate than the conventional karyotyping in clinical application. Conclusions: Although array-CGH could not detect point mutation, balanced translocations, inversions, or low-level mosaicism, the diagnosis rate in clinical application was up to 46.3% and 2.5 times that of conventional karyotyping analysis (18.1%). This study demonstrated that array-CGH is a powerful diagnostic tool and should be the first genetic test instead of conventional karyotyping analysis for patients with unexplained DD/ID. Key Words: array-CGH, chromosomal microarray, developmental delay, intellectual disabilities, Taiwanhttp://www.sciencedirect.com/science/article/pii/S1875957218302092 |
| spellingShingle | Chung-Lin Lee Chen-Hao Lee Chih-Kuang Chuang Huei-Ching Chiu Yen-Jiun Chen Chao-Ling Chou Peih-Shan Wu Chih-Ping Chen Hsiang-Yu Lin Shuan-Pei Lin Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan Pediatrics and Neonatology |
| title | Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan |
| title_full | Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan |
| title_fullStr | Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan |
| title_full_unstemmed | Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan |
| title_short | Array-CGH increased the diagnostic rate of developmental delay or intellectual disability in Taiwan |
| title_sort | array cgh increased the diagnostic rate of developmental delay or intellectual disability in taiwan |
| url | http://www.sciencedirect.com/science/article/pii/S1875957218302092 |
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