A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
Abstract Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestation...
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| Format: | Article |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07730-7 |
| _version_ | 1818343703137222656 |
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| author | Decai Wang Xinyuan Pan Jiangdong Ji Shun Gu Xiantao Sun Chao Jiang Weiyi Xia Zhihua Qiu Xiaoli Kang Sijia Ding Qinghuai Liu Xue Chen Fang Lu Chen Zhao |
| author_facet | Decai Wang Xinyuan Pan Jiangdong Ji Shun Gu Xiantao Sun Chao Jiang Weiyi Xia Zhihua Qiu Xiaoli Kang Sijia Ding Qinghuai Liu Xue Chen Fang Lu Chen Zhao |
| author_sort | Decai Wang |
| collection | DOAJ |
| description | Abstract Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestations included bilateral excavated optic disc with multiple cilioretinal vessels emerging and bilateral retinoschisis with great variability in the range of extension and severity. Other intra-familial phenotypic diversities were also noted, including severity in retinal atrophy, onset age of visual impairment and presence of congenital nystagmus and strabismus. Genome-wide linkage analysis and fine mapping mapped a novel locus for CODA to a 34.3 cM interval between D14S972 and D14S139 at 14q12-q22.1. A maximum multi-point log odds score of 3.901 was reached at D14S275. However, no mutation was identified by exome sequencing or direct sequencing of PAX6 and PAX2 genes, suggesting that the mutation may reside within a regulatory element. In conclusion, we find retinoschisis as a necessary consequence of optic nerve head (ONH) anomalies. The complicated phenotype observed in the family provided additional insights into the inherited ONH anomalies. Mapping of a novel locus, 14q12-q22.1, implies a new disease-causing gene and potential distinct pathogenesis for CODA. |
| first_indexed | 2024-12-13T16:34:48Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:34:48Z |
| publishDate | 2017-08-01 |
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| series | Scientific Reports |
| spelling | doaj.art-534a0124c6b9411088848a7b7ddce1522022-12-21T23:38:25ZengNature PortfolioScientific Reports2045-23222017-08-01711910.1038/s41598-017-07730-7A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypesDecai Wang0Xinyuan Pan1Jiangdong Ji2Shun Gu3Xiantao Sun4Chao Jiang5Weiyi Xia6Zhihua Qiu7Xiaoli Kang8Sijia Ding9Qinghuai Liu10Xue Chen11Fang Lu12Chen Zhao13Department of Preventive Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityDepartment of Ophthalmology, The Affliated Wuhu No. 2 People’s Hospital of Wannan Medical CollegeDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Ophthalmology, Wuxi People’s Hospital affiliated to Nanjing Medical UniversityDepartment of Ophthalmology, Children Hospital of ZhengzhouDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Ophthalmology, Dongyuan Hospital of traditional Chinese medicineDepartment of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Ophthalmology, West China Hospital, Sichuan UniversityDepartment of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityAbstract Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestations included bilateral excavated optic disc with multiple cilioretinal vessels emerging and bilateral retinoschisis with great variability in the range of extension and severity. Other intra-familial phenotypic diversities were also noted, including severity in retinal atrophy, onset age of visual impairment and presence of congenital nystagmus and strabismus. Genome-wide linkage analysis and fine mapping mapped a novel locus for CODA to a 34.3 cM interval between D14S972 and D14S139 at 14q12-q22.1. A maximum multi-point log odds score of 3.901 was reached at D14S275. However, no mutation was identified by exome sequencing or direct sequencing of PAX6 and PAX2 genes, suggesting that the mutation may reside within a regulatory element. In conclusion, we find retinoschisis as a necessary consequence of optic nerve head (ONH) anomalies. The complicated phenotype observed in the family provided additional insights into the inherited ONH anomalies. Mapping of a novel locus, 14q12-q22.1, implies a new disease-causing gene and potential distinct pathogenesis for CODA.https://doi.org/10.1038/s41598-017-07730-7 |
| spellingShingle | Decai Wang Xinyuan Pan Jiangdong Ji Shun Gu Xiantao Sun Chao Jiang Weiyi Xia Zhihua Qiu Xiaoli Kang Sijia Ding Qinghuai Liu Xue Chen Fang Lu Chen Zhao A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes Scientific Reports |
| title | A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes |
| title_full | A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes |
| title_fullStr | A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes |
| title_full_unstemmed | A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes |
| title_short | A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes |
| title_sort | large family with inherited optic disc anomalies a correlation between a new genetic locus and complex ocular phenotypes |
| url | https://doi.org/10.1038/s41598-017-07730-7 |
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