Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder
Abstract Background Autism spectrum disorder (ASD) is defined as a group of genetically and clinically heterogeneous neurodevelopmental disorders. Interplay between de novo and inherited rare variants has been suspected in the development of ASD. Methods Here, we applied 750K oligonucleotide microar...
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.996 |
| _version_ | 1827968014554759168 |
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| author | Ya‐Sian Chang Chien‐Yu Lin Hsi‐Yuan Huang Jan‐Gowth Chang Haung‐Tsung Kuo |
| author_facet | Ya‐Sian Chang Chien‐Yu Lin Hsi‐Yuan Huang Jan‐Gowth Chang Haung‐Tsung Kuo |
| author_sort | Ya‐Sian Chang |
| collection | DOAJ |
| description | Abstract Background Autism spectrum disorder (ASD) is defined as a group of genetically and clinically heterogeneous neurodevelopmental disorders. Interplay between de novo and inherited rare variants has been suspected in the development of ASD. Methods Here, we applied 750K oligonucleotide microarray analysis and whole‐exome sequencing (WES) to five trios from Taiwanese families with ASD. Results The chromosomal microarray analysis revealed three representative known diagnostic copy number variants that contributed to the clinical presentation: the chromosome locations 2q13, 1q21.1q21.2, and 9q33.1. WES detected 22 rare variants in all trios, including four that were newly discovered, one of which is a de novo variant. Sequencing variants of JMJD1C, TCF12, BIRC6, and NHS have not been previously reported. A novel de novo variant was identified in NHS (p.I7T). Additionally, seven pathogenic variants, including SMPD1, FUT2, BCHE, MYBPC3, DUOX2, EYS, and FLG, were detected in four probands. One of the involved genes, SMPD1, had previously been reported to be mutated in patients with Parkinson's disease. Conclusions These findings suggest that de novo or inherited rare variants and copy number variants may be double or multiple hits of the probands that lead to ASD. WES could be useful in identifying possible causative ASD variants. |
| first_indexed | 2024-04-09T18:14:37Z |
| format | Article |
| id | doaj.art-7acb078f3ceb4407aec6581db3fe3a35 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-09T18:14:37Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-7acb078f3ceb4407aec6581db3fe3a352023-04-13T05:27:13ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-12-01712n/an/a10.1002/mgg3.996Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorderYa‐Sian Chang0Chien‐Yu Lin1Hsi‐Yuan Huang2Jan‐Gowth Chang3Haung‐Tsung Kuo4Epigenome Research Center China Medical University Hospital Taichung TaiwanGraduate Institute of Clinical Medical Science and School of Medicine China Medical University Taichung TaiwanDepartment of Laboratory Medicine China Medical University Hospital Taichung TaiwanEpigenome Research Center China Medical University Hospital Taichung TaiwanDepartment of Developmental and Behavioral Pediatrics Children's Hospital of China Medical University Taichung TaiwanAbstract Background Autism spectrum disorder (ASD) is defined as a group of genetically and clinically heterogeneous neurodevelopmental disorders. Interplay between de novo and inherited rare variants has been suspected in the development of ASD. Methods Here, we applied 750K oligonucleotide microarray analysis and whole‐exome sequencing (WES) to five trios from Taiwanese families with ASD. Results The chromosomal microarray analysis revealed three representative known diagnostic copy number variants that contributed to the clinical presentation: the chromosome locations 2q13, 1q21.1q21.2, and 9q33.1. WES detected 22 rare variants in all trios, including four that were newly discovered, one of which is a de novo variant. Sequencing variants of JMJD1C, TCF12, BIRC6, and NHS have not been previously reported. A novel de novo variant was identified in NHS (p.I7T). Additionally, seven pathogenic variants, including SMPD1, FUT2, BCHE, MYBPC3, DUOX2, EYS, and FLG, were detected in four probands. One of the involved genes, SMPD1, had previously been reported to be mutated in patients with Parkinson's disease. Conclusions These findings suggest that de novo or inherited rare variants and copy number variants may be double or multiple hits of the probands that lead to ASD. WES could be useful in identifying possible causative ASD variants.https://doi.org/10.1002/mgg3.996Autism spectrum disorderChromosomal microarray analysisCopy number variantWhole‐exome sequencing |
| spellingShingle | Ya‐Sian Chang Chien‐Yu Lin Hsi‐Yuan Huang Jan‐Gowth Chang Haung‐Tsung Kuo Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder Molecular Genetics & Genomic Medicine Autism spectrum disorder Chromosomal microarray analysis Copy number variant Whole‐exome sequencing |
| title | Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder |
| title_full | Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder |
| title_fullStr | Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder |
| title_full_unstemmed | Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder |
| title_short | Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder |
| title_sort | chromosomal microarray and whole exome sequence analysis in taiwanese patients with autism spectrum disorder |
| topic | Autism spectrum disorder Chromosomal microarray analysis Copy number variant Whole‐exome sequencing |
| url | https://doi.org/10.1002/mgg3.996 |
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