Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia
Abstract Backgrounds Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort. Methods A total...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04886-5 |
| _version_ | 1797349751003283456 |
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| author | Yi Jiang Xueshan Xiao Wenmin Sun Yingwei Wang Shiqiang Li Xiaoyun Jia Panfeng Wang J. Fielding Hejtmancik Qingjiong Zhang |
| author_facet | Yi Jiang Xueshan Xiao Wenmin Sun Yingwei Wang Shiqiang Li Xiaoyun Jia Panfeng Wang J. Fielding Hejtmancik Qingjiong Zhang |
| author_sort | Yi Jiang |
| collection | DOAJ |
| description | Abstract Backgrounds Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort. Methods A total of 75 probands with simplex uHM were included in our Pediatric and Genetic Eye Clinic. Patients with significant posterior anomalies other than myopic fundus changes were excluded. Variants were detected by exome sequencing and then analyzed through multiple-step bioinformatic and co-segregation analysis and finally confirmed by Sanger sequencing. Genetic findings were correlated with associated clinical data for analysis. Results Among the 75 probands with a mean age of 6.21 ± 4.70 years at the presentation, myopic fundus of C1 and C2 was observed in 73 (97.3%) probands. Surprisingly, specific peripheral changes were identified in 63 eyes involving 36 (48.0%) probands after extensive examination, including peripheral retinal avascular zone (74.6%, 47/63 eyes), neovascularization (54.0%), fluorescein leakage (31.7%), peripheral pigmentary changes (31.7%), and others. Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage. Conclusions Genetic defects were identified in about one-fourth of simplex uHM patients in which significant consequences may be hidden under a classic myopic fundus in up to half. To our knowledge, this is the first systematic genetic study on simplex uHM to date. In addition to routine care of strabismus and amblyopia, careful examination of the peripheral retina and genetic screening is warranted for patients with uHM in order to identify signs of risk for retinal detachment and other complications and provide meaningful genetic counseling. |
| first_indexed | 2024-03-08T12:34:55Z |
| format | Article |
| id | doaj.art-e94901339c5344d6879108d96db77ae7 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-08T12:34:55Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e94901339c5344d6879108d96db77ae72024-01-21T12:33:16ZengBMCJournal of Translational Medicine1479-58762024-01-0122111810.1186/s12967-024-04886-5Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopiaYi Jiang0Xueshan Xiao1Wenmin Sun2Yingwei Wang3Shiqiang Li4Xiaoyun Jia5Panfeng Wang6J. Fielding Hejtmancik7Qingjiong Zhang8State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceOphthalmic Molecular Genetics Section, Ophthalmic Genetics and Visual Function Branch, National Eye InstituteState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceAbstract Backgrounds Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort. Methods A total of 75 probands with simplex uHM were included in our Pediatric and Genetic Eye Clinic. Patients with significant posterior anomalies other than myopic fundus changes were excluded. Variants were detected by exome sequencing and then analyzed through multiple-step bioinformatic and co-segregation analysis and finally confirmed by Sanger sequencing. Genetic findings were correlated with associated clinical data for analysis. Results Among the 75 probands with a mean age of 6.21 ± 4.70 years at the presentation, myopic fundus of C1 and C2 was observed in 73 (97.3%) probands. Surprisingly, specific peripheral changes were identified in 63 eyes involving 36 (48.0%) probands after extensive examination, including peripheral retinal avascular zone (74.6%, 47/63 eyes), neovascularization (54.0%), fluorescein leakage (31.7%), peripheral pigmentary changes (31.7%), and others. Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage. Conclusions Genetic defects were identified in about one-fourth of simplex uHM patients in which significant consequences may be hidden under a classic myopic fundus in up to half. To our knowledge, this is the first systematic genetic study on simplex uHM to date. In addition to routine care of strabismus and amblyopia, careful examination of the peripheral retina and genetic screening is warranted for patients with uHM in order to identify signs of risk for retinal detachment and other complications and provide meaningful genetic counseling.https://doi.org/10.1186/s12967-024-04886-5Unilateral high myopiaGeneticPeripheral retinal examinationAnisometropiaHigh myopia |
| spellingShingle | Yi Jiang Xueshan Xiao Wenmin Sun Yingwei Wang Shiqiang Li Xiaoyun Jia Panfeng Wang J. Fielding Hejtmancik Qingjiong Zhang Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia Journal of Translational Medicine Unilateral high myopia Genetic Peripheral retinal examination Anisometropia High myopia |
| title | Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia |
| title_full | Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia |
| title_fullStr | Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia |
| title_full_unstemmed | Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia |
| title_short | Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia |
| title_sort | clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia |
| topic | Unilateral high myopia Genetic Peripheral retinal examination Anisometropia High myopia |
| url | https://doi.org/10.1186/s12967-024-04886-5 |
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