Trio-based whole-exome sequencing reveals mutations in early-onset high myopia
Purpose Myopia, especially high myopia (HM), represents a widespread visual impairment with a globally escalating prevalence. This study aimed to elucidate the genetic foundations associated with early-onset HM (eoHM) while delineating the genetic landscape specific to Shaanxi province, China.Method...
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| Language: | English |
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BMJ Publishing Group
2024-05-01
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| Series: | BMJ Open Ophthalmology |
| Online Access: | https://bmjophth.bmj.com/content/9/1/e001720.full |
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| author | Ding Chen Xiu-Feng Huang Juan Huang Yi-Ming Guo Junhan Wei Lu Ye Yi-Xin Cai Jiejing Bi Fen-Fen Li |
| author_facet | Ding Chen Xiu-Feng Huang Juan Huang Yi-Ming Guo Junhan Wei Lu Ye Yi-Xin Cai Jiejing Bi Fen-Fen Li |
| author_sort | Ding Chen |
| collection | DOAJ |
| description | Purpose Myopia, especially high myopia (HM), represents a widespread visual impairment with a globally escalating prevalence. This study aimed to elucidate the genetic foundations associated with early-onset HM (eoHM) while delineating the genetic landscape specific to Shaanxi province, China.Methods A comprehensive analysis of whole-exome sequencing was conducted involving 26 familial trios displaying eoHM. An exacting filtration protocol identified potential candidate mutations within acknowledged myopia-related genes and susceptibility loci. Subsequently, computational methodologies were employed for functional annotations and pathogenicity assessments.Results Our investigation identified 7 genes and 10 variants associated with HM across 7 families, including a novel mutation in the ARR3 gene (c.139C>T, p.Arg47*) and two mutations in the P3H2 gene (c.1865T>C, p.Phe622Ser and c.212T>C, p.Leu71Pro). Pathogenic mutations were found in syndromic myopia genes, notably encompassing VPS13B, TRPM1, RPGR, NYX and RP2. Additionally, a thorough comparison of previously reported causative genes of syndromic myopia and myopia risk genes with the negative sequencing results pinpointed various types of mutations within risk genes.Conclusions This investigation into eoHM within Shaanxi province adds to the current understanding of myopic genetic factors. Our results warrant further functional validation and ocular examinations, yet they provide foundational insights for future genetic research and therapeutic innovations in HM. |
| format | Article |
| id | doaj-art-6c7581a96f6e4a9db689475ee9935179 |
| institution | Kabale University |
| issn | 2397-3269 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Ophthalmology |
| spelling | doaj-art-6c7581a96f6e4a9db689475ee99351792025-02-06T14:20:11ZengBMJ Publishing GroupBMJ Open Ophthalmology2397-32692024-05-019110.1136/bmjophth-2024-001720Trio-based whole-exome sequencing reveals mutations in early-onset high myopiaDing Chen0Xiu-Feng Huang1Juan Huang2Yi-Ming Guo3Junhan Wei4Lu Ye5Yi-Xin Cai6Jiejing Bi7Fen-Fen Li8National Clinical Research Center for Ocular Diseases, Wenzhou Medical University Eye Hospital, Wenzhou, Zhejiang, ChinaZhejiang Provincial Clinical Research Center for Pediatric Disease, The Second Affiliated Hospital and Yuying Children`s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaShaanxi Eye Hospital, Xi’an People’s Hospital (Xi`an Fourth Hospital), Affiliated People’s Hospital of Northwest University, Xi`an, Shaanxi, ChinaShaanxi Eye Hospital, Xi’an People’s Hospital (Xi`an Fourth Hospital), Affiliated People’s Hospital of Northwest University, Xi`an, Shaanxi, ChinaShaanxi Eye Hospital, Xi’an People’s Hospital (Xi`an Fourth Hospital), Affiliated People’s Hospital of Northwest University, Xi`an, Shaanxi, China1 Department of Oncology, Second Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, ChinaZhejiang Provincial Clinical Research Center for Pediatric Disease, The Second Affiliated Hospital and Yuying Children`s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaShaanxi Eye Hospital, Xi’an People’s Hospital (Xi`an Fourth Hospital), Affiliated People’s Hospital of Northwest University, Xi`an, Shaanxi, ChinaNational Clinical Research Center for Ocular Diseases, Wenzhou Medical University Eye Hospital, Wenzhou, Zhejiang, ChinaPurpose Myopia, especially high myopia (HM), represents a widespread visual impairment with a globally escalating prevalence. This study aimed to elucidate the genetic foundations associated with early-onset HM (eoHM) while delineating the genetic landscape specific to Shaanxi province, China.Methods A comprehensive analysis of whole-exome sequencing was conducted involving 26 familial trios displaying eoHM. An exacting filtration protocol identified potential candidate mutations within acknowledged myopia-related genes and susceptibility loci. Subsequently, computational methodologies were employed for functional annotations and pathogenicity assessments.Results Our investigation identified 7 genes and 10 variants associated with HM across 7 families, including a novel mutation in the ARR3 gene (c.139C>T, p.Arg47*) and two mutations in the P3H2 gene (c.1865T>C, p.Phe622Ser and c.212T>C, p.Leu71Pro). Pathogenic mutations were found in syndromic myopia genes, notably encompassing VPS13B, TRPM1, RPGR, NYX and RP2. Additionally, a thorough comparison of previously reported causative genes of syndromic myopia and myopia risk genes with the negative sequencing results pinpointed various types of mutations within risk genes.Conclusions This investigation into eoHM within Shaanxi province adds to the current understanding of myopic genetic factors. Our results warrant further functional validation and ocular examinations, yet they provide foundational insights for future genetic research and therapeutic innovations in HM.https://bmjophth.bmj.com/content/9/1/e001720.full |
| spellingShingle | Ding Chen Xiu-Feng Huang Juan Huang Yi-Ming Guo Junhan Wei Lu Ye Yi-Xin Cai Jiejing Bi Fen-Fen Li Trio-based whole-exome sequencing reveals mutations in early-onset high myopia BMJ Open Ophthalmology |
| title | Trio-based whole-exome sequencing reveals mutations in early-onset high myopia |
| title_full | Trio-based whole-exome sequencing reveals mutations in early-onset high myopia |
| title_fullStr | Trio-based whole-exome sequencing reveals mutations in early-onset high myopia |
| title_full_unstemmed | Trio-based whole-exome sequencing reveals mutations in early-onset high myopia |
| title_short | Trio-based whole-exome sequencing reveals mutations in early-onset high myopia |
| title_sort | trio based whole exome sequencing reveals mutations in early onset high myopia |
| url | https://bmjophth.bmj.com/content/9/1/e001720.full |
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