Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa
Abstract Background Panel‐based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. Methods A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with conf...
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| Format: | Article |
| Language: | English |
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Wiley
2020-04-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1184 |
| _version_ | 1797301079327637504 |
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| author | Yan Sun Wei Li Jian‐kang Li Zhuo‐shi Wang Jin‐yue Bai Ling Xu Bo Xing Wen Yang Zi‐wei Wang Lu‐sheng Wang Wei He Fang Chen |
| author_facet | Yan Sun Wei Li Jian‐kang Li Zhuo‐shi Wang Jin‐yue Bai Ling Xu Bo Xing Wen Yang Zi‐wei Wang Lu‐sheng Wang Wei He Fang Chen |
| author_sort | Yan Sun |
| collection | DOAJ |
| description | Abstract Background Panel‐based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. Methods A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel‐based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination. Results Of the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0–65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands. Conclusion Panel‐based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China. |
| first_indexed | 2024-03-07T23:17:16Z |
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| id | doaj.art-b8224d799d2e4818a42fee0f8d94ae76 |
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| language | English |
| last_indexed | 2024-03-07T23:17:16Z |
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| spelling | doaj.art-b8224d799d2e4818a42fee0f8d94ae762024-02-21T10:29:43ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-04-0184n/an/a10.1002/mgg3.1184Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosaYan Sun0Wei Li1Jian‐kang Li2Zhuo‐shi Wang3Jin‐yue Bai4Ling Xu5Bo Xing6Wen Yang7Zi‐wei Wang8Lu‐sheng Wang9Wei He10Fang Chen11Shenyang He Eye Specialist Hospital Shenyang ChinaHe University Shenyang ChinaBGI‐Shenzhen Shenzhen ChinaShenyang He Eye Specialist Hospital Shenyang ChinaSchool of Basic Medicine Qingdao University Qingdao ChinaShenyang He Eye Specialist Hospital Shenyang ChinaSchool of Basic Medicine Qingdao University Qingdao ChinaBGI‐Shenzhen Shenzhen ChinaBGI Education Center University of Chinese Academy of Sciences Shenzhen ChinaBGI‐Shenzhen Shenzhen ChinaShenyang He Eye Specialist Hospital Shenyang ChinaBGI‐Shenzhen Shenzhen ChinaAbstract Background Panel‐based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. Methods A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel‐based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination. Results Of the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0–65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands. Conclusion Panel‐based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China.https://doi.org/10.1002/mgg3.1184compound heterozygousdigenic inheritancepanel‐based targeted exome sequencingretinitis pigmentosa |
| spellingShingle | Yan Sun Wei Li Jian‐kang Li Zhuo‐shi Wang Jin‐yue Bai Ling Xu Bo Xing Wen Yang Zi‐wei Wang Lu‐sheng Wang Wei He Fang Chen Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa Molecular Genetics & Genomic Medicine compound heterozygous digenic inheritance panel‐based targeted exome sequencing retinitis pigmentosa |
| title | Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa |
| title_full | Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa |
| title_fullStr | Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa |
| title_full_unstemmed | Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa |
| title_short | Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa |
| title_sort | genetic and clinical findings of panel based targeted exome sequencing in a northeast chinese cohort with retinitis pigmentosa |
| topic | compound heterozygous digenic inheritance panel‐based targeted exome sequencing retinitis pigmentosa |
| url | https://doi.org/10.1002/mgg3.1184 |
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