A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy
Abstract Background Wagner vitreoretinopathy (WVR) is a rare autosomal dominant vitreoretinopathy caused by pathogenic variants in the VCAN gene. The aim of this study was to report a novel splicing variant in VCAN identified in a three‐generation Chinese family initially diagnosed with familial exu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2083 |
| _version_ | 1797903403258478592 |
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| author | Junwei Zhong Jie Shi Xiaotian Zhang Ke Xu Xiaohui Zhang Yue Xie Yang Li |
| author_facet | Junwei Zhong Jie Shi Xiaotian Zhang Ke Xu Xiaohui Zhang Yue Xie Yang Li |
| author_sort | Junwei Zhong |
| collection | DOAJ |
| description | Abstract Background Wagner vitreoretinopathy (WVR) is a rare autosomal dominant vitreoretinopathy caused by pathogenic variants in the VCAN gene. The aim of this study was to report a novel splicing variant in VCAN identified in a three‐generation Chinese family initially diagnosed with familial exudative vitreoretinopathy and to describe the patients' clinical features. Methods Four affected individuals from a three‐generation family underwent detailed ophthalmic examinations, including best‐corrected visual acuity by Snellen E chart, slit‐lamp biomicroscopy, indirect ophthalmoscopy under pupil dilatation, ocular B‐ultrasonography, optical coherence tomography scans, and fundus autofluorescence. Targeted next‐generation sequencing was performed to identify variants of the disease‐causing gene for the proband, followed by co‐segregation analysis using Sanger‐DNA sequencing. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) was carried out to verify the effects of a variant on VCAN pre‐mRNA splicing in the lymphocytes from the patients. Results We detected a novel heterozygous variant c.4004‐4_c.4004‐3delinsCA of VCAN in all four affected individuals. RT‐PCR revealed that the novel variant caused an abnormal splicing in exon 8 of the VCAN and imbalanced versican transcripts. All four patients presented vitreous syneresis and bilateral retinal detachment occurring at different ages. The patients also showed different extents of visual defects and diverse clinical manifestations, including cataract, iris–lens synechiae, inverted papillae, and ectopic foveas. Conclusions Our results expand the mutation spectrum of VCAN and further confirm that the splicing sites for exon 8 are mutation hot spots. Patients with WVR may present high phenotype variation; therefore, molecular analysis is very important for precise diagnosis of patients with inherited vitreoretinopathy. |
| first_indexed | 2024-04-10T09:32:20Z |
| format | Article |
| id | doaj.art-c25b07bf46b54463b95ac7410a8d2c4c |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-10T09:32:20Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-c25b07bf46b54463b95ac7410a8d2c4c2023-02-18T19:05:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-02-01112n/an/a10.1002/mgg3.2083A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathyJunwei Zhong0Jie Shi1Xiaotian Zhang2Ke Xu3Xiaohui Zhang4Yue Xie5Yang Li6Beijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University Beijing ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University Beijing ChinaClinical College of Ophthalmology Tianjin Medical University Tianjin ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University Beijing ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University Beijing ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University Beijing ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University Beijing ChinaAbstract Background Wagner vitreoretinopathy (WVR) is a rare autosomal dominant vitreoretinopathy caused by pathogenic variants in the VCAN gene. The aim of this study was to report a novel splicing variant in VCAN identified in a three‐generation Chinese family initially diagnosed with familial exudative vitreoretinopathy and to describe the patients' clinical features. Methods Four affected individuals from a three‐generation family underwent detailed ophthalmic examinations, including best‐corrected visual acuity by Snellen E chart, slit‐lamp biomicroscopy, indirect ophthalmoscopy under pupil dilatation, ocular B‐ultrasonography, optical coherence tomography scans, and fundus autofluorescence. Targeted next‐generation sequencing was performed to identify variants of the disease‐causing gene for the proband, followed by co‐segregation analysis using Sanger‐DNA sequencing. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) was carried out to verify the effects of a variant on VCAN pre‐mRNA splicing in the lymphocytes from the patients. Results We detected a novel heterozygous variant c.4004‐4_c.4004‐3delinsCA of VCAN in all four affected individuals. RT‐PCR revealed that the novel variant caused an abnormal splicing in exon 8 of the VCAN and imbalanced versican transcripts. All four patients presented vitreous syneresis and bilateral retinal detachment occurring at different ages. The patients also showed different extents of visual defects and diverse clinical manifestations, including cataract, iris–lens synechiae, inverted papillae, and ectopic foveas. Conclusions Our results expand the mutation spectrum of VCAN and further confirm that the splicing sites for exon 8 are mutation hot spots. Patients with WVR may present high phenotype variation; therefore, molecular analysis is very important for precise diagnosis of patients with inherited vitreoretinopathy.https://doi.org/10.1002/mgg3.2083splicing variantVCANversican transcriptsWagner vitreoretinopathy |
| spellingShingle | Junwei Zhong Jie Shi Xiaotian Zhang Ke Xu Xiaohui Zhang Yue Xie Yang Li A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy Molecular Genetics & Genomic Medicine splicing variant VCAN versican transcripts Wagner vitreoretinopathy |
| title | A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy |
| title_full | A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy |
| title_fullStr | A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy |
| title_full_unstemmed | A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy |
| title_short | A novel splicing variant of VCAN identified in a Chinese family initially diagnosed with familial exudative vitreoretinopathy |
| title_sort | novel splicing variant of vcan identified in a chinese family initially diagnosed with familial exudative vitreoretinopathy |
| topic | splicing variant VCAN versican transcripts Wagner vitreoretinopathy |
| url | https://doi.org/10.1002/mgg3.2083 |
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