SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa
The small nuclear ribonucleoprotein 200 kDa (SNRNP200) gene plays a key role in the maturation of pre-message RNA (pre-mRNA) splicing with the indication for the etiology of retinitis pigmentosa (RP). Gene recognition can facilitate the diagnosis of these patients for better clinical management, tre...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-01-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2020.588991/full |
| _version_ | 1819283235580936192 |
|---|---|
| author | Tao Zhang Tao Zhang Jingshan Bai Jingshan Bai Xinyi Zhang Xinyi Zhang Xiaowei Zheng Xiaowei Zheng Nan Lu Zhongyin Liang Ling Lin Ling Lin Yongsong Chen Yongsong Chen |
| author_facet | Tao Zhang Tao Zhang Jingshan Bai Jingshan Bai Xinyi Zhang Xinyi Zhang Xiaowei Zheng Xiaowei Zheng Nan Lu Zhongyin Liang Ling Lin Ling Lin Yongsong Chen Yongsong Chen |
| author_sort | Tao Zhang |
| collection | DOAJ |
| description | The small nuclear ribonucleoprotein 200 kDa (SNRNP200) gene plays a key role in the maturation of pre-message RNA (pre-mRNA) splicing with the indication for the etiology of retinitis pigmentosa (RP). Gene recognition can facilitate the diagnosis of these patients for better clinical management, treatment and counseling. This study aimed to outline the causative mutation in a Chinese family and the pathogenic mechanism of this SNRNP200 mutation in RP. Eighteen individuals from the affected family underwent a complete ophthalmic examination. Whole exome sequencing (WES) was conducted to identify the pathogenic variant in the proband, which was then confirmed by Sanger sequencing. Expression of the SNRNP200 transcript in zebrafish was identified via whole mount in situ hybridization. Morpholino oligonucleotide (MO) and SNRNP200 wild and mutant mRNA were injected into zebrafish embryos followed by analyses of the systemic changes and retinal phenotypes using immunofluorescence. Heterozygous SNRNP200c.C6088T (p.Arg2030Cys) mutation was ascertained in two members of this family: the proband and his father (II-2). Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WT caused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured, and significantly increased death rates in the morphant embryos, in which the orthologous zebrafish SNRNP200 gene was blocked. In conclusion, this study reports a novel heterozygous SNRNP200c.C6088T mutation, which is evidenced to cause RP via a dominant-negative effect. |
| first_indexed | 2024-12-24T01:28:16Z |
| format | Article |
| id | doaj.art-5e49b62418c54d369a769cf536186615 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-24T01:28:16Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-5e49b62418c54d369a769cf5361866152022-12-21T17:22:27ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-01-01710.3389/fmed.2020.588991588991SNRNP200 Mutations Cause Autosomal Dominant Retinitis PigmentosaTao Zhang0Tao Zhang1Jingshan Bai2Jingshan Bai3Xinyi Zhang4Xinyi Zhang5Xiaowei Zheng6Xiaowei Zheng7Nan Lu8Zhongyin Liang9Ling Lin10Ling Lin11Yongsong Chen12Yongsong Chen13Department of Ophthalmology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaThe Clinical Research Center of the First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Ophthalmology, The Second People's Hospital of Dongying, Dongying, ChinaDepartment of Ophthalmology, The Dawang Hospital of Guangrao of Dongying, Dongying, ChinaDepartment of Ophthalmology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaThe Clinical Research Center of the First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Ophthalmology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaThe Clinical Research Center of the First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Bioinformatics, Berry Genomics Co., Ltd., Beijing, ChinaThe Clinical Research Center of the First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaThe Clinical Research Center of the First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaThe small nuclear ribonucleoprotein 200 kDa (SNRNP200) gene plays a key role in the maturation of pre-message RNA (pre-mRNA) splicing with the indication for the etiology of retinitis pigmentosa (RP). Gene recognition can facilitate the diagnosis of these patients for better clinical management, treatment and counseling. This study aimed to outline the causative mutation in a Chinese family and the pathogenic mechanism of this SNRNP200 mutation in RP. Eighteen individuals from the affected family underwent a complete ophthalmic examination. Whole exome sequencing (WES) was conducted to identify the pathogenic variant in the proband, which was then confirmed by Sanger sequencing. Expression of the SNRNP200 transcript in zebrafish was identified via whole mount in situ hybridization. Morpholino oligonucleotide (MO) and SNRNP200 wild and mutant mRNA were injected into zebrafish embryos followed by analyses of the systemic changes and retinal phenotypes using immunofluorescence. Heterozygous SNRNP200c.C6088T (p.Arg2030Cys) mutation was ascertained in two members of this family: the proband and his father (II-2). Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WT caused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured, and significantly increased death rates in the morphant embryos, in which the orthologous zebrafish SNRNP200 gene was blocked. In conclusion, this study reports a novel heterozygous SNRNP200c.C6088T mutation, which is evidenced to cause RP via a dominant-negative effect.https://www.frontiersin.org/articles/10.3389/fmed.2020.588991/fullretinitis pigmentosaSNRNP200whole exome sequencingmutationmorpholino oligonucleotide |
| spellingShingle | Tao Zhang Tao Zhang Jingshan Bai Jingshan Bai Xinyi Zhang Xinyi Zhang Xiaowei Zheng Xiaowei Zheng Nan Lu Zhongyin Liang Ling Lin Ling Lin Yongsong Chen Yongsong Chen SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa Frontiers in Medicine retinitis pigmentosa SNRNP200 whole exome sequencing mutation morpholino oligonucleotide |
| title | SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa |
| title_full | SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa |
| title_fullStr | SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa |
| title_full_unstemmed | SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa |
| title_short | SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa |
| title_sort | snrnp200 mutations cause autosomal dominant retinitis pigmentosa |
| topic | retinitis pigmentosa SNRNP200 whole exome sequencing mutation morpholino oligonucleotide |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2020.588991/full |
| work_keys_str_mv | AT taozhang snrnp200mutationscauseautosomaldominantretinitispigmentosa AT taozhang snrnp200mutationscauseautosomaldominantretinitispigmentosa AT jingshanbai snrnp200mutationscauseautosomaldominantretinitispigmentosa AT jingshanbai snrnp200mutationscauseautosomaldominantretinitispigmentosa AT xinyizhang snrnp200mutationscauseautosomaldominantretinitispigmentosa AT xinyizhang snrnp200mutationscauseautosomaldominantretinitispigmentosa AT xiaoweizheng snrnp200mutationscauseautosomaldominantretinitispigmentosa AT xiaoweizheng snrnp200mutationscauseautosomaldominantretinitispigmentosa AT nanlu snrnp200mutationscauseautosomaldominantretinitispigmentosa AT zhongyinliang snrnp200mutationscauseautosomaldominantretinitispigmentosa AT linglin snrnp200mutationscauseautosomaldominantretinitispigmentosa AT linglin snrnp200mutationscauseautosomaldominantretinitispigmentosa AT yongsongchen snrnp200mutationscauseautosomaldominantretinitispigmentosa AT yongsongchen snrnp200mutationscauseautosomaldominantretinitispigmentosa |